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DISCUSSION
1
7
[ "b7" ]
16,916,791
pmid-11834782|pmid-15372043|pmid-10617568|pmid-10778853|pmid-11498593|pmid-11373684|NA|pmid-12546893|pmid-11373684
By far the most common of these is synthetic siRNA.
[ "7" ]
51
5,400
0
false
By far the most common of these is synthetic siRNA.
[]
By far the most common of these is synthetic siRNA.
true
true
true
true
true
902
0
DISCUSSION
1
7
[ "b7" ]
16,916,791
pmid-11834782|pmid-15372043|pmid-10617568|pmid-10778853|pmid-11498593|pmid-11373684|NA|pmid-12546893|pmid-11373684
These 21–23 nt RNA molecules are commonly used both in vitro and in vivo.
[ "7" ]
73
5,401
0
false
These 21–23 nt RNA molecules are commonly used both in vitro and in vivo.
[]
These 21–23 nt RNA molecules are commonly used both in vitro and in vivo.
true
true
true
true
true
902
0
DISCUSSION
1
7
[ "b7" ]
16,916,791
pmid-11834782|pmid-15372043|pmid-10617568|pmid-10778853|pmid-11498593|pmid-11373684|NA|pmid-12546893|pmid-11373684
Another form of siRNA commonly used is shRNA, which is generally expressed intracellularly from a vector.
[ "7" ]
105
5,402
0
false
Another form of siRNA commonly used is shRNA, which is generally expressed intracellularly from a vector.
[]
Another form of siRNA commonly used is shRNA, which is generally expressed intracellularly from a vector.
true
true
true
true
true
902
0
DISCUSSION
1
7
[ "b7" ]
16,916,791
pmid-11834782|pmid-15372043|pmid-10617568|pmid-10778853|pmid-11498593|pmid-11373684|NA|pmid-12546893|pmid-11373684
The use of long dsRNAs have been very limited owing to the belief that these longer regions of double stranded RNA will result in the induction of the interferon response (7).
[ "7" ]
175
5,403
1
false
The use of long dsRNAs have been very limited owing to the belief that these longer regions of double stranded RNA will result in the induction of the interferon response.
[ "7" ]
The use of long dsRNAs have been very limited owing to the belief that these longer regions of double stranded RNA will result in the induction of the interferon response.
true
true
true
true
true
902
0
DISCUSSION
1
7
[ "b7" ]
16,916,791
pmid-11834782|pmid-15372043|pmid-10617568|pmid-10778853|pmid-11498593|pmid-11373684|NA|pmid-12546893|pmid-11373684
However, the above studies demonstrate that long dsRNAs can be used to silence gene expression without inducing the stress response or causing significant off-target effects.
[ "7" ]
174
5,404
0
false
However, the above studies demonstrate that long dsRNAs can be used to silence gene expression without inducing the stress response or causing significant off-target effects.
[]
However, the above studies demonstrate that long dsRNAs can be used to silence gene expression without inducing the stress response or causing significant off-target effects.
true
true
true
true
true
902
0
DISCUSSION
1
7
[ "b7" ]
16,916,791
pmid-11834782|pmid-15372043|pmid-10617568|pmid-10778853|pmid-11498593|pmid-11373684|NA|pmid-12546893|pmid-11373684
The use of long dsRNAs can provide numerous advantages in that the cell can select the optimal silencing sequence alleviating the need to test numerous siRNAs; long dsRNAs will allow for silencing libraries to have less complexity than would be necessary for siRNAs; and, perhaps most importantly, long dsRNA could preve...
[ "7" ]
372
5,405
0
false
The use of long dsRNAs can provide numerous advantages in that the cell can select the optimal silencing sequence alleviating the need to test numerous siRNAs; long dsRNAs will allow for silencing libraries to have less complexity than would be necessary for siRNAs; and, perhaps most importantly, long dsRNA could preve...
[]
The use of long dsRNAs can provide numerous advantages in that the cell can select the optimal silencing sequence alleviating the need to test numerous siRNAs; long dsRNAs will allow for silencing libraries to have less complexity than would be necessary for siRNAs; and, perhaps most importantly, long dsRNA could preve...
true
true
true
true
true
902
1
DISCUSSION
1
28
[ "b28" ]
16,916,791
pmid-14704669|pmid-14527345|pmid-11099033|pmid-15791247|pmid-14704668|pmid-14527409|pmid-14688408|pmid-15042091|pmid-15042092|pmid-15042092|pmid-15960972|pmid-16200065|pmid-16381835|pmid-6948303
One concern with using long dsRNAs randomly generated from cDNA libraries and expressed from promoters constructed of two convergent polIII promoters is premature termination of the transcript owing to the presence of polIII terminators.
[ "28" ]
237
5,406
0
false
One concern with using long dsRNAs randomly generated from cDNA libraries and expressed from promoters constructed of two convergent polIII promoters is premature termination of the transcript owing to the presence of polIII terminators.
[]
One concern with using long dsRNAs randomly generated from cDNA libraries and expressed from promoters constructed of two convergent polIII promoters is premature termination of the transcript owing to the presence of polIII terminators.
true
true
true
true
true
903
1
DISCUSSION
1
28
[ "b28" ]
16,916,791
pmid-14704669|pmid-14527345|pmid-11099033|pmid-15791247|pmid-14704668|pmid-14527409|pmid-14688408|pmid-15042091|pmid-15042092|pmid-15042092|pmid-15960972|pmid-16200065|pmid-16381835|pmid-6948303
A long stretch of thymidine nucleotides leads to polIII termination, with a minimum of three necessary but five being optimal (28).
[ "28" ]
131
5,407
1
false
A long stretch of thymidine nucleotides leads to polIII termination, with a minimum of three necessary but five being optimal.
[ "28" ]
A long stretch of thymidine nucleotides leads to polIII termination, with a minimum of three necessary but five being optimal.
true
true
true
true
true
903
1
DISCUSSION
1
28
[ "b28" ]
16,916,791
pmid-14704669|pmid-14527345|pmid-11099033|pmid-15791247|pmid-14704668|pmid-14527409|pmid-14688408|pmid-15042091|pmid-15042092|pmid-15042092|pmid-15960972|pmid-16200065|pmid-16381835|pmid-6948303
Thus, if a terminator was present in either the sense or antisense strand very near to the promoter or if terminators for both strands were present adjacent to one another, it would be possible to generate no dsRNA.
[ "28" ]
215
5,408
0
false
Thus, if a terminator was present in either the sense or antisense strand very near to the promoter or if terminators for both strands were present adjacent to one another, it would be possible to generate no dsRNA.
[]
Thus, if a terminator was present in either the sense or antisense strand very near to the promoter or if terminators for both strands were present adjacent to one another, it would be possible to generate no dsRNA.
true
true
true
true
true
903
1
DISCUSSION
1
28
[ "b28" ]
16,916,791
pmid-14704669|pmid-14527345|pmid-11099033|pmid-15791247|pmid-14704668|pmid-14527409|pmid-14688408|pmid-15042091|pmid-15042092|pmid-15042092|pmid-15960972|pmid-16200065|pmid-16381835|pmid-6948303
It was interesting to note that the optimal long dsRNA for silencing luciferase expression was in fact, the shortest of the sequences.
[ "28" ]
134
5,409
0
false
It was interesting to note that the optimal long dsRNA for silencing luciferase expression was in fact, the shortest of the sequences.
[]
It was interesting to note that the optimal long dsRNA for silencing luciferase expression was in fact, the shortest of the sequences.
true
true
true
true
true
903
1
DISCUSSION
1
28
[ "b28" ]
16,916,791
pmid-14704669|pmid-14527345|pmid-11099033|pmid-15791247|pmid-14704668|pmid-14527409|pmid-14688408|pmid-15042091|pmid-15042092|pmid-15042092|pmid-15960972|pmid-16200065|pmid-16381835|pmid-6948303
However, when the sequence was analyzed for stretches of five thymidine nucleotides in either the forward or reverse orientation, the 250 bp sequence generates a region of ∼235 bp of dsRNA, whereas the 750 and 1000 bp sequences generate identical ∼330 bp of dsRNA and the 500 bp sequence results in a dsRNA of ∼80 bp, pe...
[ "28" ]
365
5,410
0
false
However, when the sequence was analyzed for stretches of five thymidine nucleotides in either the forward or reverse orientation, the 250 bp sequence generates a region of ∼235 bp of dsRNA, whereas the 750 and 1000 bp sequences generate identical ∼330 bp of dsRNA and the 500 bp sequence results in a dsRNA of ∼80 bp, pe...
[]
However, when the sequence was analyzed for stretches of five thymidine nucleotides in either the forward or reverse orientation, the 250 bp sequence generates a region of ∼235 bp of dsRNA, whereas the 750 and 1000 bp sequences generate identical ∼330 bp of dsRNA and the 500 bp sequence results in a dsRNA of ∼80 bp, pe...
true
true
true
true
true
903
1
DISCUSSION
1
28
[ "b28" ]
16,916,791
pmid-14704669|pmid-14527345|pmid-11099033|pmid-15791247|pmid-14704668|pmid-14527409|pmid-14688408|pmid-15042091|pmid-15042092|pmid-15042092|pmid-15960972|pmid-16200065|pmid-16381835|pmid-6948303
These results demostrate that while the existance of polIII terminators may prevent some dsRNAs from forming, a stretch of five thymidines should occur on average once every 1000 bp so the likelihood that such stretches will occur on opposite strands of a 250 nt base pair digestion product is remote.
[ "28" ]
301
5,411
0
false
These results demostrate that while the existance of polIII terminators may prevent some dsRNAs from forming, a stretch of five thymidines should occur on average once every 1000 bp so the likelihood that such stretches will occur on opposite strands of a 250 nt base pair digestion product is remote.
[]
These results demostrate that while the existance of polIII terminators may prevent some dsRNAs from forming, a stretch of five thymidines should occur on average once every 1000 bp so the likelihood that such stretches will occur on opposite strands of a 250 nt base pair digestion product is remote.
true
true
true
true
true
903
1
DISCUSSION
1
28
[ "b28" ]
16,916,791
pmid-14704669|pmid-14527345|pmid-11099033|pmid-15791247|pmid-14704668|pmid-14527409|pmid-14688408|pmid-15042091|pmid-15042092|pmid-15042092|pmid-15960972|pmid-16200065|pmid-16381835|pmid-6948303
In addition, it is extremely unlikely that if a cDNA was digested to numerous 250 bp fragments, every fragment would contain terminators preventing formation of dsRNAs.
[ "28" ]
168
5,412
0
false
In addition, it is extremely unlikely that if a cDNA was digested to numerous 250 bp fragments, every fragment would contain terminators preventing formation of dsRNAs.
[]
In addition, it is extremely unlikely that if a cDNA was digested to numerous 250 bp fragments, every fragment would contain terminators preventing formation of dsRNAs.
true
true
true
true
true
903
1
DISCUSSION
1
28
[ "b28" ]
16,916,791
pmid-14704669|pmid-14527345|pmid-11099033|pmid-15791247|pmid-14704668|pmid-14527409|pmid-14688408|pmid-15042091|pmid-15042092|pmid-15042092|pmid-15960972|pmid-16200065|pmid-16381835|pmid-6948303
Thus, use of random 250 bp regions should result in effective silencing.
[ "28" ]
72
5,413
0
false
Thus, use of random 250 bp regions should result in effective silencing.
[]
Thus, use of random 250 bp regions should result in effective silencing.
true
true
true
true
true
903
2
DISCUSSION
1
29
[ "b29", "b9", "b30", "b32", "b7", "b33", "b34", "b35", "b38" ]
16,916,791
pmid-14704668|pmid-15534205|pmid-14684833|pmid-11724966|pmid-12546893|pmid-9335428|pmid-1357546|pmid-11373684|pmid-12942087|pmid-12796781|NA|pmid-15327987
Long dsRNAs are capable of undergoing dicer-mediated processing to siRNAs in mammalian cells resulting in the production of numerous siRNAs of 22–23 nt (29).
[ "29", "9", "30", "32", "7", "33", "34", "35", "38" ]
157
5,414
1
false
Long dsRNAs are capable of undergoing dicer-mediated processing to siRNAs in mammalian cells resulting in the production of numerous siRNAs of 22–23 nt.
[ "29" ]
Long dsRNAs are capable of undergoing dicer-mediated processing to siRNAs in mammalian cells resulting in the production of numerous siRNAs of 22–23 nt.
true
true
true
true
true
904
2
DISCUSSION
1
9
[ "b29", "b9", "b30", "b32", "b7", "b33", "b34", "b35", "b38" ]
16,916,791
pmid-14704668|pmid-15534205|pmid-14684833|pmid-11724966|pmid-12546893|pmid-9335428|pmid-1357546|pmid-11373684|pmid-12942087|pmid-12796781|NA|pmid-15327987
The presence of numerous fragments against a single target has the advantage of allowing the cell to select the most efficient siRNA for target accessibility and by producing numerous dsRNAs, can offer better potential therapeutic protection against viral infections by making resistance difficult (9).
[ "29", "9", "30", "32", "7", "33", "34", "35", "38" ]
302
5,415
1
false
The presence of numerous fragments against a single target has the advantage of allowing the cell to select the most efficient siRNA for target accessibility and by producing numerous dsRNAs, can offer better potential therapeutic protection against viral infections by making resistance difficult.
[ "9" ]
The presence of numerous fragments against a single target has the advantage of allowing the cell to select the most efficient siRNA for target accessibility and by producing numerous dsRNAs, can offer better potential therapeutic protection against viral infections by making resistance difficult.
true
true
true
true
true
904
2
DISCUSSION
1
7
[ "b29", "b9", "b30", "b32", "b7", "b33", "b34", "b35", "b38" ]
16,916,791
pmid-14704668|pmid-15534205|pmid-14684833|pmid-11724966|pmid-12546893|pmid-9335428|pmid-1357546|pmid-11373684|pmid-12942087|pmid-12796781|NA|pmid-15327987
However, there has been a long standing belief that long dsRNAs induce an interferon response, beginning with dsRNA viruses induction of a stress response (30–32) and further supported when early work comparing long dsRNA with siRNAs was carried out (7).
[ "29", "9", "30", "32", "7", "33", "34", "35", "38" ]
254
5,416
1
false
However, there has been a long standing belief that long dsRNAs induce an interferon response, beginning with dsRNA viruses induction of a stress response and further supported when early work comparing long dsRNA with siRNAs was carried out.
[ "30–32", "7" ]
However, there has been a long standing belief that long dsRNAs induce an interferon response, beginning with dsRNA viruses induction of a stress response and further supported when early work comparing long dsRNA with siRNAs was carried out.
true
true
true
true
true
904
2
DISCUSSION
1
29
[ "b29", "b9", "b30", "b32", "b7", "b33", "b34", "b35", "b38" ]
16,916,791
pmid-14704668|pmid-15534205|pmid-14684833|pmid-11724966|pmid-12546893|pmid-9335428|pmid-1357546|pmid-11373684|pmid-12942087|pmid-12796781|NA|pmid-15327987
These studies are often cited as rationale for working with siRNAs but other studies have reported that siRNA can also induce an interferon response in mammalian cells (33,34).
[ "29", "9", "30", "32", "7", "33", "34", "35", "38" ]
176
5,417
0
false
These studies are often cited as rationale for working with siRNAs but other studies have reported that siRNA can also induce an interferon response in mammalian cells.
[ "33,34" ]
These studies are often cited as rationale for working with siRNAs but other studies have reported that siRNA can also induce an interferon response in mammalian cells.
true
true
true
true
true
904
2
DISCUSSION
1
29
[ "b29", "b9", "b30", "b32", "b7", "b33", "b34", "b35", "b38" ]
16,916,791
pmid-14704668|pmid-15534205|pmid-14684833|pmid-11724966|pmid-12546893|pmid-9335428|pmid-1357546|pmid-11373684|pmid-12942087|pmid-12796781|NA|pmid-15327987
Although siRNAs are still the method of choice for silencing gene expression, there have been a number of reports in which long dsRNAs have been used in mammalian cells and in mammals without signs of toxicity or adverse effects on the animal (35–38).
[ "29", "9", "30", "32", "7", "33", "34", "35", "38" ]
251
5,418
0
false
Although siRNAs are still the method of choice for silencing gene expression, there have been a number of reports in which long dsRNAs have been used in mammalian cells and in mammals without signs of toxicity or adverse effects on the animal.
[ "35–38" ]
Although siRNAs are still the method of choice for silencing gene expression, there have been a number of reports in which long dsRNAs have been used in mammalian cells and in mammals without signs of toxicity or adverse effects on the animal.
true
true
true
true
true
904
2
DISCUSSION
1
29
[ "b29", "b9", "b30", "b32", "b7", "b33", "b34", "b35", "b38" ]
16,916,791
pmid-14704668|pmid-15534205|pmid-14684833|pmid-11724966|pmid-12546893|pmid-9335428|pmid-1357546|pmid-11373684|pmid-12942087|pmid-12796781|NA|pmid-15327987
The lack of interferon response associated with long dsRNA in this study was an encouraging first step in the development of libraries since long dsRNA would reduce the required complexity and allow processing to numerous siRNAs intracellularly, enhancing the probability of target acessibility.
[ "29", "9", "30", "32", "7", "33", "34", "35", "38" ]
295
5,419
0
false
The lack of interferon response associated with long dsRNA in this study was an encouraging first step in the development of libraries since long dsRNA would reduce the required complexity and allow processing to numerous siRNAs intracellularly, enhancing the probability of target acessibility.
[]
The lack of interferon response associated with long dsRNA in this study was an encouraging first step in the development of libraries since long dsRNA would reduce the required complexity and allow processing to numerous siRNAs intracellularly, enhancing the probability of target acessibility.
true
true
true
true
true
904
3
DISCUSSION
1
29
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
A second important consideration when using long dsRNA is the potential for significant off-target silencing.
[ "29", "39", "40", "41", "42", "43" ]
109
5,420
0
false
A second important consideration when using long dsRNA is the potential for significant off-target silencing.
[]
A second important consideration when using long dsRNA is the potential for significant off-target silencing.
true
true
true
true
true
905
3
DISCUSSION
1
29
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
One of the proposed strengths of an siRNA is that the 21–23 bp sequence can be analyzed against the genomic database and identical matches can be avoided.
[ "29", "39", "40", "41", "42", "43" ]
154
5,421
0
false
One of the proposed strengths of an siRNA is that the 21–23 bp sequence can be analyzed against the genomic database and identical matches can be avoided.
[]
One of the proposed strengths of an siRNA is that the 21–23 bp sequence can be analyzed against the genomic database and identical matches can be avoided.
true
true
true
true
true
905
3
DISCUSSION
1
29
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
This becomes difficult, if not impossible, when using a 250 bp dsRNA that will be processed into a number of potential overlapping 21–23 bp siRNAs (29).
[ "29", "39", "40", "41", "42", "43" ]
152
5,422
1
false
This becomes difficult, if not impossible, when using a 250 bp dsRNA that will be processed into a number of potential overlapping 21–23 bp siRNAs.
[ "29" ]
This becomes difficult, if not impossible, when using a 250 bp dsRNA that will be processed into a number of potential overlapping 21–23 bp siRNAs.
true
true
true
true
true
905
3
DISCUSSION
1
29
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
One of the real strengths of siRNAs was originally thought to be the exquisite specificity of the interaction.
[ "29", "39", "40", "41", "42", "43" ]
110
5,423
0
false
One of the real strengths of siRNAs was originally thought to be the exquisite specificity of the interaction.
[]
One of the real strengths of siRNAs was originally thought to be the exquisite specificity of the interaction.
true
true
true
true
true
905
3
DISCUSSION
1
39
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
When a reporter gene, GFP, was used as a target to assess silencing ot the reporter expression in HEK293 cells, no detectable secondary effects were noted by genomewide expression profiling (39) with a similar profiling demonstrating high specificity when the profiles of three endogenous genes were compared (40).
[ "29", "39", "40", "41", "42", "43" ]
314
5,424
1
false
When a reporter gene, GFP, was used as a target to assess silencing ot the reporter expression in HEK293 cells, no detectable secondary effects were noted by genomewide expression profiling with a similar profiling demonstrating high specificity when the profiles of three endogenous genes were compared.
[ "39", "40" ]
When a reporter gene, GFP, was used as a target to assess silencing ot the reporter expression in HEK293 cells, no detectable secondary effects were noted by genomewide expression profiling with a similar profiling demonstrating high specificity when the profiles of three endogenous genes were compared.
true
true
true
true
true
905
3
DISCUSSION
1
41
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
The tremendous specificity of the response was also inferred from data generated using siRNAs as antiviral treatments—resistant viruses were shown to contain a single nucleotide substitution in the region corresponding to the sequence of the siRNA (41).
[ "29", "39", "40", "41", "42", "43" ]
253
5,425
1
false
The tremendous specificity of the response was also inferred from data generated using siRNAs as antiviral treatments—resistant viruses were shown to contain a single nucleotide substitution in the region corresponding to the sequence of the siRNA.
[ "41" ]
The tremendous specificity of the response was also inferred from data generated using siRNAs as antiviral treatments—resistant viruses were shown to contain a single nucleotide substitution in the region corresponding to the sequence of the siRNA.
true
true
true
true
true
905
3
DISCUSSION
1
29
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
More recently, this specificity has come into question.
[ "29", "39", "40", "41", "42", "43" ]
55
5,426
0
false
More recently, this specificity has come into question.
[]
More recently, this specificity has come into question.
true
true
true
true
true
905
3
DISCUSSION
1
42
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
When similar expression profiling was carried out using multiple siRNAs against a MAPK14 or IGF1R, there were reproducible expression patterns for each siRNA across three experiments but a set of siRNAs against a given target found only a few genes regulated similarly for the given target (42).
[ "29", "39", "40", "41", "42", "43" ]
295
5,427
1
false
When similar expression profiling was carried out using multiple siRNAs against a MAPK14 or IGF1R, there were reproducible expression patterns for each siRNA across three experiments but a set of siRNAs against a given target found only a few genes regulated similarly for the given target.
[ "42" ]
When similar expression profiling was carried out using multiple siRNAs against a MAPK14 or IGF1R, there were reproducible expression patterns for each siRNA across three experiments but a set of siRNAs against a given target found only a few genes regulated similarly for the given target.
true
true
true
true
true
905
3
DISCUSSION
1
29
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
This was unexpected since siRNAs targeting the same gene should result in the same changes in an expression profile.
[ "29", "39", "40", "41", "42", "43" ]
116
5,428
0
false
This was unexpected since siRNAs targeting the same gene should result in the same changes in an expression profile.
[]
This was unexpected since siRNAs targeting the same gene should result in the same changes in an expression profile.
true
true
true
true
true
905
3
DISCUSSION
1
29
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
They also reported that the observed off-target effects could not be titrated out using lower concentrations of siRNA and that an siRNA targeting luciferase reproducibly silenced other genes in the absence of any sequence similarity.
[ "29", "39", "40", "41", "42", "43" ]
233
5,429
0
false
They also reported that the observed off-target effects could not be titrated out using lower concentrations of siRNA and that an siRNA targeting luciferase reproducibly silenced other genes in the absence of any sequence similarity.
[]
They also reported that the observed off-target effects could not be titrated out using lower concentrations of siRNA and that an siRNA targeting luciferase reproducibly silenced other genes in the absence of any sequence similarity.
true
true
true
true
true
905
3
DISCUSSION
1
43
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
In another study, a 21 bp siRNA against luciferase was also found to elicit significant off-target effects, stimulating or repressing >1000 genes (43).
[ "29", "39", "40", "41", "42", "43" ]
151
5,430
1
false
In another study, a 21 bp siRNA against luciferase was also found to elicit significant off-target effects, stimulating or repressing >1000 genes.
[ "43" ]
In another study, a 21 bp siRNA against luciferase was also found to elicit significant off-target effects, stimulating or repressing >1000 genes.
true
true
true
true
true
905
3
DISCUSSION
1
29
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
They explained this, at least in part, through the induction of the stress response through the PKR pathway.
[ "29", "39", "40", "41", "42", "43" ]
108
5,431
0
false
They explained this, at least in part, through the induction of the stress response through the PKR pathway.
[]
They explained this, at least in part, through the induction of the stress response through the PKR pathway.
true
true
true
true
true
905
3
DISCUSSION
1
29
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
In light of these latter studies, the several hundred genes identified by expression analysis in this study that exhibit an increase or decrease following silencing of luciferase with long dsRNA were not unexpected for silencing in general.
[ "29", "39", "40", "41", "42", "43" ]
240
5,432
0
false
In light of these latter studies, the several hundred genes identified by expression analysis in this study that exhibit an increase or decrease following silencing of luciferase with long dsRNA were not unexpected for silencing in general.
[]
In light of these latter studies, the several hundred genes identified by expression analysis in this study that exhibit an increase or decrease following silencing of luciferase with long dsRNA were not unexpected for silencing in general.
true
true
true
true
true
905
3
DISCUSSION
1
29
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
Although the effectiveness of the luciferase could not be monitored on the array since its sequence was not present on the array, analysis of luciferase expression in a popultion of cells transfected at the same time and in the same way demonstrated the on-target efficacy of the dsRNA (data not shown).
[ "29", "39", "40", "41", "42", "43" ]
303
5,433
0
false
Although the effectiveness of the luciferase could not be monitored on the array since its sequence was not present on the array, analysis of luciferase expression in a popultion of cells transfected at the same time and in the same way demonstrated the on-target efficacy of the dsRNA (data not shown).
[]
Although the effectiveness of the luciferase could not be monitored on the array since its sequence was not present on the array, analysis of luciferase expression in a popultion of cells transfected at the same time and in the same way demonstrated the on-target efficacy of the dsRNA (data not shown).
true
true
true
true
true
905
3
DISCUSSION
1
29
[ "b29", "b39", "b40", "b41", "b42", "b43" ]
16,916,791
pmid-11724966|pmid-12730368|pmid-12746500|pmid-12087357|pmid-12754523|pmid-14681580
From these results, long dsRNAs do not appear to be toxic and the non-specific effects are modest when compared with those of siRNAs.
[ "29", "39", "40", "41", "42", "43" ]
133
5,434
0
false
From these results, long dsRNAs do not appear to be toxic and the non-specific effects are modest when compared with those of siRNAs.
[]
From these results, long dsRNAs do not appear to be toxic and the non-specific effects are modest when compared with those of siRNAs.
true
true
true
true
true
905
4
DISCUSSION
1
44
[ "b44", "b45", "b45", "b46" ]
16,916,791
pmid-11250734|pmid-12888360|pmid-12888360|pmid-10647931
We next tested whether a long dsRNA expressed from a plasmid would not only silence gene expression but would also result in the desired phenotypic change.
[ "44", "45", "45", "46" ]
155
5,435
0
false
We next tested whether a long dsRNA expressed from a plasmid would not only silence gene expression but would also result in the desired phenotypic change.
[]
We next tested whether a long dsRNA expressed from a plasmid would not only silence gene expression but would also result in the desired phenotypic change.
true
true
true
true
true
906
4
DISCUSSION
1
44
[ "b44", "b45", "b45", "b46" ]
16,916,791
pmid-11250734|pmid-12888360|pmid-12888360|pmid-10647931
To analyze this activity we choose to attempt to inhibit cell migration as a strategy for targeting cancer metastasis.
[ "44", "45", "45", "46" ]
118
5,436
0
false
To analyze this activity we choose to attempt to inhibit cell migration as a strategy for targeting cancer metastasis.
[]
To analyze this activity we choose to attempt to inhibit cell migration as a strategy for targeting cancer metastasis.
true
true
true
true
true
906
4
DISCUSSION
1
44
[ "b44", "b45", "b45", "b46" ]
16,916,791
pmid-11250734|pmid-12888360|pmid-12888360|pmid-10647931
The understanding of how a primary tumor cell migrates from the initial tumor, disperses throughout the body in the vascular/lymphatic system, invades a new site and begins to proliferate and form secondary tumors in not well understood (44), although it is well accepted that the mechanisms leading to metastases will r...
[ "44", "45", "45", "46" ]
365
5,437
1
false
The understanding of how a primary tumor cell migrates from the initial tumor, disperses throughout the body in the vascular/lymphatic system, invades a new site and begins to proliferate and form secondary tumors in not well understood, although it is well accepted that the mechanisms leading to metastases will repres...
[ "44", "45" ]
The understanding of how a primary tumor cell migrates from the initial tumor, disperses throughout the body in the vascular/lymphatic system, invades a new site and begins to proliferate and form secondary tumors in not well understood, although it is well accepted that the mechanisms leading to metastases will repres...
true
true
true
true
true
906
4
DISCUSSION
1
44
[ "b44", "b45", "b45", "b46" ]
16,916,791
pmid-11250734|pmid-12888360|pmid-12888360|pmid-10647931
Since migration and invasion are key components of cellular metastasis (45,46), these processes have been well studied in cell culture systems and represent an attractive model to look at the functional effects of large dsRNAs.
[ "44", "45", "45", "46" ]
227
5,438
0
false
Since migration and invasion are key components of cellular metastasis, these processes have been well studied in cell culture systems and represent an attractive model to look at the functional effects of large dsRNAs.
[ "45,46" ]
Since migration and invasion are key components of cellular metastasis, these processes have been well studied in cell culture systems and represent an attractive model to look at the functional effects of large dsRNAs.
true
true
true
true
true
906
5
DISCUSSION
1
27
[ "b27", "b47", "b48", "b49", "b50", "b51" ]
16,916,791
pmid-15520203|pmid-14613995|pmid-15264243|pmid-15922853|pmid-14617781|pmid-15949770
Recently, an siRNA to c-met has been identified and shown to lead to apoptosis and reduction of tumor growth (27).
[ "27", "47", "48", "49", "50", "51" ]
114
5,439
1
false
Recently, an siRNA to c-met has been identified and shown to lead to apoptosis and reduction of tumor growth.
[ "27" ]
Recently, an siRNA to c-met has been identified and shown to lead to apoptosis and reduction of tumor growth.
true
true
true
true
true
907
5
DISCUSSION
1
27
[ "b27", "b47", "b48", "b49", "b50", "b51" ]
16,916,791
pmid-15520203|pmid-14613995|pmid-15264243|pmid-15922853|pmid-14617781|pmid-15949770
In addition, when c-met was knocked-down using ribozymes, cell invasion and metastasis were inhibited both in vitro and in mice (47,48).
[ "27", "47", "48", "49", "50", "51" ]
136
5,440
0
false
In addition, when c-met was knocked-down using ribozymes, cell invasion and metastasis were inhibited both in vitro and in mice.
[ "47,48" ]
In addition, when c-met was knocked-down using ribozymes, cell invasion and metastasis were inhibited both in vitro and in mice.
true
true
true
true
true
907
5
DISCUSSION
1
51
[ "b27", "b47", "b48", "b49", "b50", "b51" ]
16,916,791
pmid-15520203|pmid-14613995|pmid-15264243|pmid-15922853|pmid-14617781|pmid-15949770
A number of groups are targeting c-met for therapeutic intervention with small molecules (49,50) given its important role in tumor metastasis (51).
[ "27", "47", "48", "49", "50", "51" ]
147
5,441
1
false
A number of groups are targeting c-met for therapeutic intervention with small molecules given its important role in tumor metastasis.
[ "49,50", "51" ]
A number of groups are targeting c-met for therapeutic intervention with small molecules given its important role in tumor metastasis.
true
true
true
true
true
907
5
DISCUSSION
1
27
[ "b27", "b47", "b48", "b49", "b50", "b51" ]
16,916,791
pmid-15520203|pmid-14613995|pmid-15264243|pmid-15922853|pmid-14617781|pmid-15949770
For these reasons, c-met was used in the present studies as a positive control dsRNA for cell invasion.
[ "27", "47", "48", "49", "50", "51" ]
103
5,442
0
false
For these reasons, c-met was used in the present studies as a positive control dsRNA for cell invasion.
[]
For these reasons, c-met was used in the present studies as a positive control dsRNA for cell invasion.
true
true
true
true
true
907
5
DISCUSSION
1
27
[ "b27", "b47", "b48", "b49", "b50", "b51" ]
16,916,791
pmid-15520203|pmid-14613995|pmid-15264243|pmid-15922853|pmid-14617781|pmid-15949770
When comparing the dsRNA with the previously reported siRNA, both inhibited cell migration to an identical level.
[ "27", "47", "48", "49", "50", "51" ]
113
5,443
0
false
When comparing the dsRNA with the previously reported siRNA, both inhibited cell migration to an identical level.
[]
When comparing the dsRNA with the previously reported siRNA, both inhibited cell migration to an identical level.
true
true
true
true
true
907
5
DISCUSSION
1
27
[ "b27", "b47", "b48", "b49", "b50", "b51" ]
16,916,791
pmid-15520203|pmid-14613995|pmid-15264243|pmid-15922853|pmid-14617781|pmid-15949770
To determine whether this inhibition was owing to the transfection of the plasmid containing the dsRNA for c-met, the migrating and non-migrating populations of cells were compared.
[ "27", "47", "48", "49", "50", "51" ]
181
5,444
0
false
To determine whether this inhibition was owing to the transfection of the plasmid containing the dsRNA for c-met, the migrating and non-migrating populations of cells were compared.
[]
To determine whether this inhibition was owing to the transfection of the plasmid containing the dsRNA for c-met, the migrating and non-migrating populations of cells were compared.
true
true
true
true
true
907
5
DISCUSSION
1
27
[ "b27", "b47", "b48", "b49", "b50", "b51" ]
16,916,791
pmid-15520203|pmid-14613995|pmid-15264243|pmid-15922853|pmid-14617781|pmid-15949770
While a plasmid expressing dsRNA against luciferase was found in equal abundance in the two populations of cells, the plasmid expressing dsRNA against c-met was enriched almost 4-fold in the non-migrating cell population.
[ "27", "47", "48", "49", "50", "51" ]
221
5,445
0
false
While a plasmid expressing dsRNA against luciferase was found in equal abundance in the two populations of cells, the plasmid expressing dsRNA against c-met was enriched almost 4-fold in the non-migrating cell population.
[]
While a plasmid expressing dsRNA against luciferase was found in equal abundance in the two populations of cells, the plasmid expressing dsRNA against c-met was enriched almost 4-fold in the non-migrating cell population.
true
true
true
true
true
907
5
DISCUSSION
1
27
[ "b27", "b47", "b48", "b49", "b50", "b51" ]
16,916,791
pmid-15520203|pmid-14613995|pmid-15264243|pmid-15922853|pmid-14617781|pmid-15949770
This enrichment is consistent with the loss of c-met function, which should result in inhibition of migration.
[ "27", "47", "48", "49", "50", "51" ]
110
5,446
0
false
This enrichment is consistent with the loss of c-met function, which should result in inhibition of migration.
[]
This enrichment is consistent with the loss of c-met function, which should result in inhibition of migration.
true
true
true
true
true
907
5
DISCUSSION
1
27
[ "b27", "b47", "b48", "b49", "b50", "b51" ]
16,916,791
pmid-15520203|pmid-14613995|pmid-15264243|pmid-15922853|pmid-14617781|pmid-15949770
Thus, these studies demonstrate the ability to silence an endogenous gene and obtain the desired phenotype.
[ "27", "47", "48", "49", "50", "51" ]
107
5,447
0
false
Thus, these studies demonstrate the ability to silence an endogenous gene and obtain the desired phenotype.
[]
Thus, these studies demonstrate the ability to silence an endogenous gene and obtain the desired phenotype.
true
true
true
true
true
907
5
DISCUSSION
1
27
[ "b27", "b47", "b48", "b49", "b50", "b51" ]
16,916,791
pmid-15520203|pmid-14613995|pmid-15264243|pmid-15922853|pmid-14617781|pmid-15949770
The presence of c-met dsRNA plasmid in the migrating population of cells may represent low number of copies per cell resulting in low levels of dsRNA that are insufficient to elicit the change in migration or may represent a population of the MDA-MD-231 cells whose migration is not dependent on c-met expression.
[ "27", "47", "48", "49", "50", "51" ]
313
5,448
0
false
The presence of c-met dsRNA plasmid in the migrating population of cells may represent low number of copies per cell resulting in low levels of dsRNA that are insufficient to elicit the change in migration or may represent a population of the MDA-MD-231 cells whose migration is not dependent on c-met expression.
[]
The presence of c-met dsRNA plasmid in the migrating population of cells may represent low number of copies per cell resulting in low levels of dsRNA that are insufficient to elicit the change in migration or may represent a population of the MDA-MD-231 cells whose migration is not dependent on c-met expression.
true
true
true
true
true
907
5
DISCUSSION
1
27
[ "b27", "b47", "b48", "b49", "b50", "b51" ]
16,916,791
pmid-15520203|pmid-14613995|pmid-15264243|pmid-15922853|pmid-14617781|pmid-15949770
A further analysis of this population would be required to better understand the biological significance of this phenomenon.
[ "27", "47", "48", "49", "50", "51" ]
124
5,449
0
false
A further analysis of this population would be required to better understand the biological significance of this phenomenon.
[]
A further analysis of this population would be required to better understand the biological significance of this phenomenon.
true
true
true
true
true
907
6
DISCUSSION
0
null
null
16,916,791
null
Results from these studies have demonstrated the ability of dsRNA to silence endogenous gene expression, leading to a biological response, without inducing an interferon response or significant off-target effects.
null
213
5,450
0
false
null
null
Results from these studies have demonstrated the ability of dsRNA to silence endogenous gene expression, leading to a biological response, without inducing an interferon response or significant off-target effects.
true
true
true
true
true
908
6
DISCUSSION
0
null
null
16,916,791
null
This is the first step in creating functional dsRNA libraries.
null
62
5,451
0
false
null
null
This is the first step in creating functional dsRNA libraries.
true
true
true
true
true
908
6
DISCUSSION
0
null
null
16,916,791
null
Using long dsRNAs, libraries can be generated from cells expressing a phenotype of interest and transfected back into the same type of cells to look for loss of function.
null
170
5,452
0
false
null
null
Using long dsRNAs, libraries can be generated from cells expressing a phenotype of interest and transfected back into the same type of cells to look for loss of function.
true
true
true
true
true
908
6
DISCUSSION
0
null
null
16,916,791
null
The dsRNA sequence resulting in loss of function can then be rescued, sequenced and the isolated sequence further tested for function.
null
134
5,453
0
false
null
null
The dsRNA sequence resulting in loss of function can then be rescued, sequenced and the isolated sequence further tested for function.
true
true
true
true
true
908
6
DISCUSSION
0
null
null
16,916,791
null
The use of long dsRNAs also offer promise for development of therapeutics, particularly since off-target effects are modest when compared with those found with siRNAs.
null
167
5,454
0
false
null
null
The use of long dsRNAs also offer promise for development of therapeutics, particularly since off-target effects are modest when compared with those found with siRNAs.
true
true
true
true
true
908
0
INTRODUCTION
1
1
[ "b1", "b3" ]
17,151,076
pmid-10357856|pmid-12102557|pmid-11344258|pmid-12727883|pmid-11149954|pmid-12853609|pmid-15241417|pmid-15665873
The 3′ end processing of mRNAs is an essential step in the maturation of eukaryotic transcripts.
[ "1", "3" ]
96
5,455
0
false
The 3′ end processing of mRNAs is an essential step in the maturation of eukaryotic transcripts.
[]
The 3′ end processing of mRNAs is an essential step in the maturation of eukaryotic transcripts.
true
true
true
true
true
909
0
INTRODUCTION
1
1
[ "b1", "b3" ]
17,151,076
pmid-10357856|pmid-12102557|pmid-11344258|pmid-12727883|pmid-11149954|pmid-12853609|pmid-15241417|pmid-15665873
In this orchestrated process, an initial site-specific cleavage in the 3′-untranslated region (3′-UTR) of the nascent mRNA is followed by the addition and subsequent trimming of a homopolymeric polyadenylate tail.
[ "1", "3" ]
213
5,456
0
false
In this orchestrated process, an initial site-specific cleavage in the 3′-untranslated region of the nascent mRNA is followed by the addition and subsequent trimming of a homopolymeric polyadenylate tail.
[ "3′-UTR" ]
In this orchestrated process, an initial site-specific cleavage in the 3′-untranslated region of the nascent mRNA is followed by the addition and subsequent trimming of a homopolymeric polyadenylate tail.
true
true
true
true
true
909
0
INTRODUCTION
1
1
[ "b1", "b3" ]
17,151,076
pmid-10357856|pmid-12102557|pmid-11344258|pmid-12727883|pmid-11149954|pmid-12853609|pmid-15241417|pmid-15665873
The assembly of processing factors at the poly(A) site stimulates transcriptional termination through interaction with the transcription machinery, whilst addition and trimming of the poly(A) tail is important for regulating mRNA stability, efficient nuclear export and subsequent translation, reviewed (1–3).
[ "1", "3" ]
309
5,457
0
false
The assembly of processing factors at the poly(A) site stimulates transcriptional termination through interaction with the transcription machinery, whilst addition and trimming of the poly(A) tail is important for regulating mRNA stability, efficient nuclear export and subsequent translation, reviewed.
[ "1–3" ]
The assembly of processing factors at the poly(A) site stimulates transcriptional termination through interaction with the transcription machinery, whilst addition and trimming of the poly(A) tail is important for regulating mRNA stability, efficient nuclear export and subsequent translation, reviewed.
true
true
true
true
true
909
1
INTRODUCTION
1
1
[ "b1", "b4", "b5", "b6", "b7", "b8", "b9", "b10", "b11" ]
17,151,076
pmid-10357856|pmid-9009831|pmid-1508215|pmid-9889288|pmid-1848175|pmid-7565751|pmid-11406596|pmid-3568131|pmid-16542450|pmid-12727883
The 3′ end processing events in Saccharomyces cerevisiae are co-ordinated by a series of conserved RNA sequence elements located in the 3′-UTR around the site of transcript cleavage (1,4).
[ "1", "4", "5", "6", "7", "8", "9", "10", "11" ]
188
5,458
0
false
The 3′ end processing events in Saccharomyces cerevisiae are co-ordinated by a series of conserved RNA sequence elements located in the 3′-UTR around the site of transcript cleavage.
[ "1,4" ]
The 3′ end processing events in Saccharomyces cerevisiae are co-ordinated by a series of conserved RNA sequence elements located in the 3′-UTR around the site of transcript cleavage.
true
true
true
true
true
910
1
INTRODUCTION
1
5
[ "b1", "b4", "b5", "b6", "b7", "b8", "b9", "b10", "b11" ]
17,151,076
pmid-10357856|pmid-9009831|pmid-1508215|pmid-9889288|pmid-1848175|pmid-7565751|pmid-11406596|pmid-3568131|pmid-16542450|pmid-12727883
The first of these is the cleavage/poly(A) site itself, that comprises a pyrimidine base followed by a run of adenines (PyAn) (5).
[ "1", "4", "5", "6", "7", "8", "9", "10", "11" ]
130
5,459
1
false
The first of these is the cleavage/poly(A) site itself, that comprises a pyrimidine base followed by a run of adenines (PyAn).
[ "5" ]
The first of these is the cleavage/poly(A) site itself, that comprises a pyrimidine base followed by a run of adenines (PyAn).
true
true
true
true
true
910
1
INTRODUCTION
1
6
[ "b1", "b4", "b5", "b6", "b7", "b8", "b9", "b10", "b11" ]
17,151,076
pmid-10357856|pmid-9009831|pmid-1508215|pmid-9889288|pmid-1848175|pmid-7565751|pmid-11406596|pmid-3568131|pmid-16542450|pmid-12727883
A series of UA repeats located at a variable number of nucleotides 5′ to the cleavage site constitutes the efficiency element (EE) (6) and an A-rich sequence located ∼20 nt 5′ to the cleavage site is termed the positioning element (PE) (7,8).
[ "1", "4", "5", "6", "7", "8", "9", "10", "11" ]
242
5,460
1
false
A series of UA repeats located at a variable number of nucleotides 5′ to the cleavage site constitutes the efficiency element (EE) and an A-rich sequence located ∼20 nt 5′ to the cleavage site is termed the positioning element (PE).
[ "6", "7,8" ]
A series of UA repeats located at a variable number of nucleotides 5′ to the cleavage site constitutes the efficiency element (EE) and an A-rich sequence located ∼20 nt 5′ to the cleavage site is termed the positioning element (PE).
true
true
true
true
true
910
1
INTRODUCTION
1
9
[ "b1", "b4", "b5", "b6", "b7", "b8", "b9", "b10", "b11" ]
17,151,076
pmid-10357856|pmid-9009831|pmid-1508215|pmid-9889288|pmid-1848175|pmid-7565751|pmid-11406596|pmid-3568131|pmid-16542450|pmid-12727883
The polyadenylation site is also frequently surrounded by upstream and downstream U-rich regions that affect the efficiency of cleavage and polyadenylation (9).
[ "1", "4", "5", "6", "7", "8", "9", "10", "11" ]
160
5,461
1
false
The polyadenylation site is also frequently surrounded by upstream and downstream U-rich regions that affect the efficiency of cleavage and polyadenylation.
[ "9" ]
The polyadenylation site is also frequently surrounded by upstream and downstream U-rich regions that affect the efficiency of cleavage and polyadenylation.
true
true
true
true
true
910
1
INTRODUCTION
1
1
[ "b1", "b4", "b5", "b6", "b7", "b8", "b9", "b10", "b11" ]
17,151,076
pmid-10357856|pmid-9009831|pmid-1508215|pmid-9889288|pmid-1848175|pmid-7565751|pmid-11406596|pmid-3568131|pmid-16542450|pmid-12727883
In mammals, the 3′-UTRs of mRNAs contain similar, but not identical conserved recognition elements.
[ "1", "4", "5", "6", "7", "8", "9", "10", "11" ]
99
5,462
0
false
In mammals, the 3′-UTRs of mRNAs contain similar, but not identical conserved recognition elements.
[]
In mammals, the 3′-UTRs of mRNAs contain similar, but not identical conserved recognition elements.
true
true
true
true
true
910
1
INTRODUCTION
1
1
[ "b1", "b4", "b5", "b6", "b7", "b8", "b9", "b10", "b11" ]
17,151,076
pmid-10357856|pmid-9009831|pmid-1508215|pmid-9889288|pmid-1848175|pmid-7565751|pmid-11406596|pmid-3568131|pmid-16542450|pmid-12727883
The major difference being the presence of a GU- and U-rich elements located 10–30 nt downstream of the polyadenylation site (10,11).
[ "1", "4", "5", "6", "7", "8", "9", "10", "11" ]
133
5,463
0
false
The major difference being the presence of a GU- and U-rich elements located 10–30 nt downstream of the polyadenylation site.
[ "10,11" ]
The major difference being the presence of a GU- and U-rich elements located 10–30 nt downstream of the polyadenylation site.
true
true
true
true
true
910
2
INTRODUCTION
1
12
[ "b12", "b13", "b14", "b15", "b16", "b17", "b18", "b19" ]
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
In S.cerevisiae, at least 24 proteins have been identified that are required in combination with the 3′-UTR RNA sequence elements to carry out efficient and high-fidelity transcript cleavage, polyadenylation and trimming.
[ "12", "13", "14", "15", "16", "17", "18", "19" ]
221
5,464
0
false
In S.cerevisiae, at least 24 proteins have been identified that are required in combination with the 3′-UTR RNA sequence elements to carry out efficient and high-fidelity transcript cleavage, polyadenylation and trimming.
[]
In S.cerevisiae, at least 24 proteins have been identified that are required in combination with the 3′-UTR RNA sequence elements to carry out efficient and high-fidelity transcript cleavage, polyadenylation and trimming.
true
true
true
true
true
911
2
INTRODUCTION
1
12
[ "b12", "b13", "b14", "b15", "b16", "b17", "b18", "b19" ]
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
These 24 proteins constitute three multiprotein complexes; cleavage factor IA (CFIA), cleavage and polyadenylation factor (CPF), poly(A) nuclease (PAN) together with poly(A) polymerase (Pap1) and three other associated factors Hrp1, Pab1 and Pbp1.
[ "12", "13", "14", "15", "16", "17", "18", "19" ]
247
5,465
0
false
These 24 proteins constitute three multiprotein complexes; cleavage factor IA (CFIA), cleavage and polyadenylation factor (CPF), poly(A) nuclease (PAN) together with poly(A) polymerase (Pap1) and three other associated factors Hrp1, Pab1 and Pbp1.
[]
These 24 proteins constitute three multiprotein complexes; cleavage factor IA (CFIA), cleavage and polyadenylation factor (CPF), poly(A) nuclease (PAN) together with poly(A) polymerase and three other associated factors Hrp1, Pab1 and Pbp1.
true
true
true
true
true
911
2
INTRODUCTION
1
12
[ "b12", "b13", "b14", "b15", "b16", "b17", "b18", "b19" ]
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
CFIA is required for both transcript cleavage and polyadenylation (12).
[ "12", "13", "14", "15", "16", "17", "18", "19" ]
71
5,466
1
false
CFIA is required for both transcript cleavage and polyadenylation.
[ "12" ]
CFIA is required for both transcript cleavage and polyadenylation.
true
true
true
true
true
911
2
INTRODUCTION
1
12
[ "b12", "b13", "b14", "b15", "b16", "b17", "b18", "b19" ]
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
The complex is comprised of four core subunits Rna14, Rna15, Pcf11 and Clp1 but can be co-purified with the associated factor, Hrp1 (13,14).
[ "12", "13", "14", "15", "16", "17", "18", "19" ]
140
5,467
0
false
The complex is comprised of four core subunits Rna14, Rna15, Pcf11 and Clp1 but can be co-purified with the associated factor, Hrp1.
[ "13,14" ]
The complex is comprised of four core subunits Rna14, Rna15, Pcf11 and Clp1 but can be co-purified with the associated factor, Hrp1.
true
true
true
true
true
911
2
INTRODUCTION
1
12
[ "b12", "b13", "b14", "b15", "b16", "b17", "b18", "b19" ]
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
CPF is also required in both the cleavage and polyadenylation reactions.
[ "12", "13", "14", "15", "16", "17", "18", "19" ]
72
5,468
0
false
CPF is also required in both the cleavage and polyadenylation reactions.
[]
CPF is also required in both the cleavage and polyadenylation reactions.
true
true
true
true
true
911
2
INTRODUCTION
1
15
[ "b12", "b13", "b14", "b15", "b16", "b17", "b18", "b19" ]
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
It contains a core of eight subunits Cft1, Cft2, Ysh1, Pta1 Mpe1, Pfs2, Fip1 and Yth1 (15).
[ "12", "13", "14", "15", "16", "17", "18", "19" ]
91
5,469
1
false
It contains a core of eight subunits Cft1, Cft2, Ysh1, Pta1 Mpe1, Pfs2, Fip1 and Yth1.
[ "15" ]
It contains a core of eight subunits Cft1, Cft2, Ysh1, Pta1 Mpe1, Pfs2, Fip1 and Yth1.
true
true
true
true
true
911
2
INTRODUCTION
1
16
[ "b12", "b13", "b14", "b15", "b16", "b17", "b18", "b19" ]
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
However a larger complex has been identified holo-CPF that contains an additional six subunits Ref2, Pti1, Swd2, Glc7, Ssu72 and Syc1 (16).
[ "12", "13", "14", "15", "16", "17", "18", "19" ]
139
5,470
1
false
However a larger complex has been identified holo-CPF that contains an additional six subunits Ref2, Pti1, Swd2, Glc7, Ssu72 and Syc1.
[ "16" ]
However a larger complex has been identified holo-CPF that contains an additional six subunits Ref2, Pti1, Swd2, Glc7, Ssu72 and Syc1.
true
true
true
true
true
911
2
INTRODUCTION
1
12
[ "b12", "b13", "b14", "b15", "b16", "b17", "b18", "b19" ]
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
Pap1 is required for addition of the poly(A) tail and PAN, consisting of Pan2 nuclease and Pan3 regulatory proteins, is the 3′–5′ PAN responsible for trimming newly formed poly(A) tails (17,18).
[ "12", "13", "14", "15", "16", "17", "18", "19" ]
194
5,471
0
false
Pap1 is required for addition of the poly(A) tail and PAN, consisting of Pan2 nuclease and Pan3 regulatory proteins, is the 3′–5′ PAN responsible for trimming newly formed poly(A) tails.
[ "17,18" ]
Pap1 is required for addition of the poly(A) tail and PAN, consisting of Pan2 nuclease and Pan3 regulatory proteins, is the 3′–5′ PAN responsible for trimming newly formed poly(A) tails.
true
true
true
true
true
911
2
INTRODUCTION
1
19
[ "b12", "b13", "b14", "b15", "b16", "b17", "b18", "b19" ]
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
PAN activity is also regulated by the Pbp1 and Pab1 associated factors (19).
[ "12", "13", "14", "15", "16", "17", "18", "19" ]
76
5,472
1
false
PAN activity is also regulated by the Pbp1 and Pab1 associated factors.
[ "19" ]
PAN activity is also regulated by the Pbp1 and Pab1 associated factors.
true
true
true
true
true
911
3
INTRODUCTION
1
9
[ "b9", "b20", "b21", "b22", "b23", "b24" ]
17,151,076
pmid-11406596|pmid-10899131|pmid-12145212|pmid-9776761|pmid-9334319|pmid-11689695
Although the molecular mechanism of 3′ end processing is poorly understood, several of the protein–RNA interactions involved in the process has been identified.
[ "9", "20", "21", "22", "23", "24" ]
160
5,473
0
false
Although the molecular mechanism of 3′ end processing is poorly understood, several of the protein–RNA interactions involved in the process has been identified.
[]
Although the molecular mechanism of 3′ end processing is poorly understood, several of the protein–RNA interactions involved in the process has been identified.
true
true
true
true
true
912
3
INTRODUCTION
1
24
[ "b9", "b20", "b21", "b22", "b23", "b24" ]
17,151,076
pmid-11406596|pmid-10899131|pmid-12145212|pmid-9776761|pmid-9334319|pmid-11689695
The CPF subunits Cft1, Cft2 and Yth1 bind the U-rich RNA sequences around the poly(A) site (9,20,21), Hrp1 binds to the EE (22,23) and through association with CFIA helps tether Rna15 to the PE (24).
[ "9", "20", "21", "22", "23", "24" ]
199
5,474
1
false
The CPF subunits Cft1, Cft2 and Yth1 bind the U-rich RNA sequences around the poly(A) site, Hrp1 binds to the EE and through association with CFIA helps tether Rna15 to the PE.
[ "9,20,21", "22,23", "24" ]
The CPF subunits Cft1, Cft2 and Yth1 bind the U-rich RNA sequences around the poly(A) site, Hrp1 binds to the EE and through association with CFIA helps tether Rna15 to the PE.
true
true
true
true
true
912
4
INTRODUCTION
1
13
[ "b13", "b14", "b23", "b25", "b14", "b26", "b27", "b27", "b14", "b28", "b30", "b30", "b34" ]
17,151,076
pmid-8900210|pmid-11344258|pmid-9334319|pmid-15215336|pmid-11344258|pmid-10619842|pmid-12853609|pmid-12853609|pmid-11344258|pmid-9032237|pmid-12727883|pmid-12727883|pmid-15665873|pmid-1352851|pmid-9857200|pmid-9099738
Alongside these protein–RNA interactions, numerous protein–protein interactions between CFIA subunits have been identified together with inter-complex CF1A–CPF interactions indicating a large degree of crosstalk between these complexes.
[ "13", "14", "23", "25", "14", "26", "27", "27", "14", "28", "30", "30", "34" ]
236
5,475
0
false
Alongside these protein–RNA interactions, numerous protein–protein interactions between CFIA subunits have been identified together with inter-complex CF1A–CPF interactions indicating a large degree of crosstalk between these complexes.
[]
Alongside these protein–RNA interactions, numerous protein–protein interactions between CFIA subunits have been identified together with inter-complex CF1A–CPF interactions indicating a large degree of crosstalk between these complexes.
true
true
true
true
true
913
4
INTRODUCTION
1
13
[ "b13", "b14", "b23", "b25", "b14", "b26", "b27", "b27", "b14", "b28", "b30", "b30", "b34" ]
17,151,076
pmid-8900210|pmid-11344258|pmid-9334319|pmid-15215336|pmid-11344258|pmid-10619842|pmid-12853609|pmid-12853609|pmid-11344258|pmid-9032237|pmid-12727883|pmid-12727883|pmid-15665873|pmid-1352851|pmid-9857200|pmid-9099738
Specifically, Rna15 is tightly associated with Rna14 (13,14,23,25).
[ "13", "14", "23", "25", "14", "26", "27", "27", "14", "28", "30", "30", "34" ]
67
5,476
0
false
Specifically, Rna15 is tightly associated with Rna14.
[ "13,14,23,25" ]
Specifically, Rna15 is tightly associated with Rna14.
true
true
true
true
true
913
4
INTRODUCTION
1
14
[ "b13", "b14", "b23", "b25", "b14", "b26", "b27", "b27", "b14", "b28", "b30", "b30", "b34" ]
17,151,076
pmid-8900210|pmid-11344258|pmid-9334319|pmid-15215336|pmid-11344258|pmid-10619842|pmid-12853609|pmid-12853609|pmid-11344258|pmid-9032237|pmid-12727883|pmid-12727883|pmid-15665873|pmid-1352851|pmid-9857200|pmid-9099738
Rna14 can further associate with Pcf11 and Hrp1 (14) and also binds the Pfs2 and Cft1 subunits of CPF (26,27).
[ "13", "14", "23", "25", "14", "26", "27", "27", "14", "28", "30", "30", "34" ]
110
5,477
1
false
Rna14 can further associate with Pcf11 and Hrp1 and also binds the Pfs2 and Cft1 subunits of CPF.
[ "14", "26,27" ]
Rna14 can further associate with Pcf11 and Hrp1 and also binds the Pfs2 and Cft1 subunits of CPF.
true
true
true
true
true
913
4
INTRODUCTION
1
14
[ "b13", "b14", "b23", "b25", "b14", "b26", "b27", "b27", "b14", "b28", "b30", "b30", "b34" ]
17,151,076
pmid-8900210|pmid-11344258|pmid-9334319|pmid-15215336|pmid-11344258|pmid-10619842|pmid-12853609|pmid-12853609|pmid-11344258|pmid-9032237|pmid-12727883|pmid-12727883|pmid-15665873|pmid-1352851|pmid-9857200|pmid-9099738
Pcf11 binds the CPF components Cft1, Cft2, Ysh1 and Pta1 (27) as well as being associated with all of the other CFIA subunits (14).
[ "13", "14", "23", "25", "14", "26", "27", "27", "14", "28", "30", "30", "34" ]
131
5,478
1
false
Pcf11 binds the CPF components Cft1, Cft2, Ysh1 and Pta1 as well as being associated with all of the other CFIA subunits.
[ "27", "14" ]
Pcf11 binds the CPF components Cft1, Cft2, Ysh1 and Pta1 as well as being associated with all of the other CFIA subunits.
true
true
true
true
true
913
4
INTRODUCTION
1
13
[ "b13", "b14", "b23", "b25", "b14", "b26", "b27", "b27", "b14", "b28", "b30", "b30", "b34" ]
17,151,076
pmid-8900210|pmid-11344258|pmid-9334319|pmid-15215336|pmid-11344258|pmid-10619842|pmid-12853609|pmid-12853609|pmid-11344258|pmid-9032237|pmid-12727883|pmid-12727883|pmid-15665873|pmid-1352851|pmid-9857200|pmid-9099738
The binding sites of Rna14/Rna15 and Clp1 have been mapped by two-hybrid analysis to a central region within Pcf11 that also contains two putative zinc-finger motifs (28–30).
[ "13", "14", "23", "25", "14", "26", "27", "27", "14", "28", "30", "30", "34" ]
174
5,479
0
false
The binding sites of Rna14/Rna15 and Clp1 have been mapped by two-hybrid analysis to a central region within Pcf11 that also contains two putative zinc-finger motifs.
[ "28–30" ]
The binding sites of Rna14/Rna15 and Clp1 have been mapped by two-hybrid analysis to a central region within Pcf11 that also contains two putative zinc-finger motifs.
true
true
true
true
true
913
4
INTRODUCTION
1
13
[ "b13", "b14", "b23", "b25", "b14", "b26", "b27", "b27", "b14", "b28", "b30", "b30", "b34" ]
17,151,076
pmid-8900210|pmid-11344258|pmid-9334319|pmid-15215336|pmid-11344258|pmid-10619842|pmid-12853609|pmid-12853609|pmid-11344258|pmid-9032237|pmid-12727883|pmid-12727883|pmid-15665873|pmid-1352851|pmid-9857200|pmid-9099738
Located at the N-terminus, Pcf11 contains a CTD interaction domain (CID) that binds to the phosphorylated heptapeptide repeats within the C-terminal domain of the largest subunit of RNA polymerase II and couples 3′ end processing to transcription (30–34).
[ "13", "14", "23", "25", "14", "26", "27", "27", "14", "28", "30", "30", "34" ]
255
5,480
0
false
Located at the N-terminus, Pcf11 contains a CTD interaction domain (CID) that binds to the phosphorylated heptapeptide repeats within the C-terminal domain of the largest subunit of RNA polymerase II and couples 3′ end processing to transcription.
[ "30–34" ]
Located at the N-terminus, Pcf11 contains a CTD interaction domain (CID) that binds to the phosphorylated heptapeptide repeats within the C-terminal domain of the largest subunit of RNA polymerase II and couples 3′ end processing to transcription.
true
true
true
true
true
913
5
INTRODUCTION
1
35
[ "b35", "b36", "b14", "b27", "b37", "b39", "b35" ]
17,151,076
pmid-11060040|pmid-6329717|pmid-11344258|pmid-12853609|pmid-12177301|pmid-16213211|pmid-11060040|pmid-11848849|pmid-15458408|pmid-15635448
The Clp1 component of CFIA displays a degree of evolutionary conservation and homologues have been identified in eukaryotes ranging from yeasts to humans (35).
[ "35", "36", "14", "27", "37", "39", "35" ]
159
5,481
1
false
The Clp1 component of CFIA displays a degree of evolutionary conservation and homologues have been identified in eukaryotes ranging from yeasts to humans.
[ "35" ]
The Clp1 component of CFIA displays a degree of evolutionary conservation and homologues have been identified in eukaryotes ranging from yeasts to humans.
true
true
true
true
true
914
5
INTRODUCTION
1
36
[ "b35", "b36", "b14", "b27", "b37", "b39", "b35" ]
17,151,076
pmid-11060040|pmid-6329717|pmid-11344258|pmid-12853609|pmid-12177301|pmid-16213211|pmid-11060040|pmid-11848849|pmid-15458408|pmid-15635448
This conserved sequence includes a Walker A motif (36), typically found in adenine or guanine nucleotide binding proteins suggesting that Clp1 function may involve nucleotide binding or catalysis.
[ "35", "36", "14", "27", "37", "39", "35" ]
196
5,482
1
false
This conserved sequence includes a Walker A motif, typically found in adenine or guanine nucleotide binding proteins suggesting that Clp1 function may involve nucleotide binding or catalysis.
[ "36" ]
This conserved sequence includes a Walker A motif, typically found in adenine or guanine nucleotide binding proteins suggesting that Clp1 function may involve nucleotide binding or catalysis.
true
true
true
true
true
914
5
INTRODUCTION
1
14
[ "b35", "b36", "b14", "b27", "b37", "b39", "b35" ]
17,151,076
pmid-11060040|pmid-6329717|pmid-11344258|pmid-12853609|pmid-12177301|pmid-16213211|pmid-11060040|pmid-11848849|pmid-15458408|pmid-15635448
In S.cerevisiae it has been demonstrated that Clp1 binds to Pcf11 but not to the other CFIA subunits (14) and that Clp1 also associates with the Ysh1 subunit of CPF (27) proposed to be the endonuclease responsible for transcript cleavage (37–39).
[ "35", "36", "14", "27", "37", "39", "35" ]
246
5,483
1
false
In S.cerevisiae it has been demonstrated that Clp1 binds to Pcf11 but not to the other CFIA subunits and that Clp1 also associates with the Ysh1 subunit of CPF proposed to be the endonuclease responsible for transcript cleavage.
[ "14", "27", "37–39" ]
In S.cerevisiae it has been demonstrated that Clp1 binds to Pcf11 but not to the other CFIA subunits and that Clp1 also associates with the Ysh1 subunit of CPF proposed to be the endonuclease responsible for transcript cleavage.
true
true
true
true
true
914
5
INTRODUCTION
1
35
[ "b35", "b36", "b14", "b27", "b37", "b39", "b35" ]
17,151,076
pmid-11060040|pmid-6329717|pmid-11344258|pmid-12853609|pmid-12177301|pmid-16213211|pmid-11060040|pmid-11848849|pmid-15458408|pmid-15635448
Similarly, in the humans, hClp1 is associated with hPcf11 as part of the CFIIm (mammalian cleavage factor II) complex were it is proposed that Clp1 function may involve bridging CFIIm to the other mammalian 3′ end processing complexes CPSF (CPF), and CFIm (cleavage factor I) (35).
[ "35", "36", "14", "27", "37", "39", "35" ]
281
5,484
1
false
Similarly, in the humans, hClp1 is associated with hPcf11 as part of the CFIIm (mammalian cleavage factor II) complex were it is proposed that Clp1 function may involve bridging CFIIm to the other mammalian 3′ end processing complexes CPSF (CPF), and CFIm (cleavage factor I).
[ "35" ]
Similarly, in the humans, hClp1 is associated with hPcf11 as part of the CFIIm (mammalian cleavage factor II) complex were it is proposed that Clp1 function may involve bridging CFIIm to the other mammalian 3′ end processing complexes CPSF (CPF), and CFIm (cleavage factor I).
true
true
true
true
true
914
6
INTRODUCTION
1
40
[ "b40" ]
17,151,076
pmid-11916378|pmid-12853609|pmid-12177301|pmid-16213211|pmid-11060040
Here, we report the structure of a ternary complex of Clp1-ATP and the Clp1-binding region of Pcf11.
[ "40" ]
100
5,485
0
false
Here, we report the structure of a ternary complex of Clp1-ATP and the Clp1-binding region of Pcf11.
[]
Here, we report the structure of a ternary complex of Clp1-ATP and the Clp1-binding region of Pcf11.
true
true
true
true
true
915
6
INTRODUCTION
1
40
[ "b40" ]
17,151,076
pmid-11916378|pmid-12853609|pmid-12177301|pmid-16213211|pmid-11060040
Because key residues from Pcf11 that are involved in the protein–protein interface are highly conserved across eukaryotes it follows that this Clp1–Pcf11 interaction is a feature common to all 3′ end processing complexes.
[ "40" ]
221
5,486
0
false
Because key residues from Pcf11 that are involved in the protein–protein interface are highly conserved across eukaryotes it follows that this Clp1–Pcf11 interaction is a feature common to all 3′ end processing complexes.
[]
Because key residues from Pcf11 that are involved in the protein–protein interface are highly conserved across eukaryotes it follows that this Clp1–Pcf11 interaction is a feature common to all 3′ end processing complexes.
true
true
true
true
true
915
6
INTRODUCTION
1
40
[ "b40" ]
17,151,076
pmid-11916378|pmid-12853609|pmid-12177301|pmid-16213211|pmid-11060040
The ATP is bound to Clp1 at a site containing a canonical P-loop together with the switch regions commonly associated with SIMIBI-class ATP/GTPases (40).
[ "40" ]
153
5,487
1
false
The ATP is bound to Clp1 at a site containing a canonical P-loop together with the switch regions commonly associated with SIMIBI-class ATP/GTPases.
[ "40" ]
The ATP is bound to Clp1 at a site containing a canonical P-loop together with the switch regions commonly associated with SIMIBI-class ATP/GTPases.
true
true
true
true
true
915
6
INTRODUCTION
1
40
[ "b40" ]
17,151,076
pmid-11916378|pmid-12853609|pmid-12177301|pmid-16213211|pmid-11060040
Nevertheless, we have been unable to detect Clp1 mediated nucleotide hydrolysis even though the geometry of the ATP-binding site and orientation of the switch loops share a strong similarity with the active site of ATPase subunits found as part of other multimeric complexes.
[ "40" ]
275
5,488
0
false
Nevertheless, we have been unable to detect Clp1 mediated nucleotide hydrolysis even though the geometry of the ATP-binding site and orientation of the switch loops share a strong similarity with the active site of ATPase subunits found as part of other multimeric complexes.
[]
Nevertheless, we have been unable to detect Clp1 mediated nucleotide hydrolysis even though the geometry of the ATP-binding site and orientation of the switch loops share a strong similarity with the active site of ATPase subunits found as part of other multimeric complexes.
true
true
true
true
true
915
6
INTRODUCTION
1
40
[ "b40" ]
17,151,076
pmid-11916378|pmid-12853609|pmid-12177301|pmid-16213211|pmid-11060040
In light of these data, we present a model where CFIA-CPF association is required to stimulate the ATPase activity of Clp1 in order to transmit conformational effects through 3′ end processing factors bound at the polyadenylation signal sequences.
[ "40" ]
247
5,489
0
false
In light of these data, we present a model where CFIA-CPF association is required to stimulate the ATPase activity of Clp1 in order to transmit conformational effects through 3′ end processing factors bound at the polyadenylation signal sequences.
[]
In light of these data, we present a model where CFIA-CPF association is required to stimulate the ATPase activity of Clp1 in order to transmit conformational effects through 3′ end processing factors bound at the polyadenylation signal sequences.
true
true
true
true
true
915
0
DISCUSSION
1
14
[ "b14", "b30", "b32", "b27", "b33", "b34" ]
17,151,076
pmid-10357856|pmid-12102557|pmid-11344258|pmid-12727883|pmid-11149954|pmid-12853609|pmid-15241417|pmid-15665873
Pcf11 interacts directly with all the other CFIA components (14) and links the cleavage-polyadenylation machinery to the transcriptional elongation complex by coupling CFIA to the phosphorylated CtD of RNA polymerase (30–32).
[ "14", "30", "32", "27", "33", "34" ]
225
5,490
1
false
Pcf11 interacts directly with all the other CFIA components and links the cleavage-polyadenylation machinery to the transcriptional elongation complex by coupling CFIA to the phosphorylated CtD of RNA polymerase.
[ "14", "30–32" ]
Pcf11 interacts directly with all the other CFIA components and links the cleavage-polyadenylation machinery to the transcriptional elongation complex by coupling CFIA to the phosphorylated CtD of RNA polymerase.
true
true
true
true
true
916
0
DISCUSSION
1
27
[ "b14", "b30", "b32", "b27", "b33", "b34" ]
17,151,076
pmid-10357856|pmid-12102557|pmid-11344258|pmid-12727883|pmid-11149954|pmid-12853609|pmid-15241417|pmid-15665873
Furthermore, Pcf11 also binds to several components of other 3′ end processing complexes (27) so it seems likely that part of Pcf11 function is to coordinate cross talk between CFIA, RNA polymerase and the other polyadenylation factors.
[ "14", "30", "32", "27", "33", "34" ]
236
5,491
1
false
Furthermore, Pcf11 also binds to several components of other 3′ end processing complexes so it seems likely that part of Pcf11 function is to coordinate cross talk between CFIA, RNA polymerase and the other polyadenylation factors.
[ "27" ]
Furthermore, Pcf11 also binds to several components of other 3′ end processing complexes so it seems likely that part of Pcf11 function is to coordinate cross talk between CFIA, RNA polymerase and the other polyadenylation factors.
true
true
true
true
true
916
0
DISCUSSION
1
14
[ "b14", "b30", "b32", "b27", "b33", "b34" ]
17,151,076
pmid-10357856|pmid-12102557|pmid-11344258|pmid-12727883|pmid-11149954|pmid-12853609|pmid-15241417|pmid-15665873
The nature of the Pcf11 interaction with the CtD of RNA polymerase is well understood (33,34) and now our data have provided the molecular details of the interaction of Pcf11 with another one of its binding partners, Clp1.
[ "14", "30", "32", "27", "33", "34" ]
222
5,492
0
false
The nature of the Pcf11 interaction with the CtD of RNA polymerase is well understood and now our data have provided the molecular details of the interaction of Pcf11 with another one of its binding partners, Clp1.
[ "33,34" ]
The nature of the Pcf11 interaction with the CtD of RNA polymerase is well understood and now our data have provided the molecular details of the interaction of Pcf11 with another one of its binding partners, Clp1.
true
true
true
true
true
916
1
DISCUSSION
1
30
[ "b30" ]
17,151,076
pmid-10357856|pmid-9009831|pmid-1508215|pmid-9889288|pmid-1848175|pmid-7565751|pmid-11406596|pmid-3568131|pmid-16542450|pmid-12727883
The Clp1-binding domain of Pcf11 consists of a region of around 25 amino acids (residues 475–499).
[ "30" ]
98
5,493
0
false
The Clp1-binding domain of Pcf11 consists of a region of around 25 amino acids (residues 475–499).
[]
The Clp1-binding domain of Pcf11 consists of a region of around 25 amino acids (residues 475–499).
true
true
true
true
true
917
1
DISCUSSION
1
30
[ "b30" ]
17,151,076
pmid-10357856|pmid-9009831|pmid-1508215|pmid-9889288|pmid-1848175|pmid-7565751|pmid-11406596|pmid-3568131|pmid-16542450|pmid-12727883
This short stretch of sequence is located between the two putative zinc-finger motifs found in the primary sequence of Pcf11 and overlaps the Clp1-binding domain that has previously been proposed from yeast two-hybrid analyses (30).
[ "30" ]
232
5,494
1
false
This short stretch of sequence is located between the two putative zinc-finger motifs found in the primary sequence of Pcf11 and overlaps the Clp1-binding domain that has previously been proposed from yeast two-hybrid analyses.
[ "30" ]
This short stretch of sequence is located between the two putative zinc-finger motifs found in the primary sequence of Pcf11 and overlaps the Clp1-binding domain that has previously been proposed from yeast two-hybrid analyses.
true
true
true
true
true
917
1
DISCUSSION
1
30
[ "b30" ]
17,151,076
pmid-10357856|pmid-9009831|pmid-1508215|pmid-9889288|pmid-1848175|pmid-7565751|pmid-11406596|pmid-3568131|pmid-16542450|pmid-12727883
As the fragment of Pcf11 used to form the complex was much larger, spanning residues 454 to 563 and we observe no interaction with residues outside this region, it seems likely that this peptide forms a large proportion if not the entire Clp1-binding interface of Pcf11.
[ "30" ]
270
5,495
0
false
As the fragment of Pcf11 used to form the complex was much larger, spanning residues 454 to 563 and we observe no interaction with residues outside this region, it seems likely that this peptide forms a large proportion if not the entire Clp1-binding interface of Pcf11.
[]
As the fragment of Pcf11 used to form the complex was much larger, spanning residues 454 to 563 and we observe no interaction with residues outside this region, it seems likely that this peptide forms a large proportion if not the entire Clp1-binding interface of Pcf11.
true
true
true
true
true
917
2
DISCUSSION
0
null
null
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
The protein–protein interface is made up from both polar and apolar interactions and for such a short stretch of sequence the total amount of buried surface at the interface is reasonably extensive (1580 Å2).
null
208
5,496
0
false
null
null
The protein–protein interface is made up from both polar and apolar interactions and for such a short stretch of sequence the total amount of buried surface at the interface is reasonably extensive (1580 Å2).
true
true
true
true
true
918
2
DISCUSSION
0
null
null
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
Moreover, this region of Pcf11 contains three conserved residues R480, W482 and W489 that are all involved in hydrogen bonding and/or hydrophobic interactions at the protein–protein interface.
null
192
5,497
0
false
null
null
Moreover, this region of Pcf11 contains three conserved residues R480, W482 and W489 that are all involved in hydrogen bonding and/or hydrophobic interactions at the protein–protein interface.
true
true
true
true
true
918
2
DISCUSSION
0
null
null
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
Taken together, these observations show that this Clp1–Pcf11 interaction is not transient and that the Clp1–Pcf11 heterodimer is a stable subcomplex of CFIA.
null
157
5,498
0
false
null
null
Taken together, these observations show that this Clp1–Pcf11 interaction is not transient and that the Clp1–Pcf11 heterodimer is a stable subcomplex of CFIA.
true
true
true
true
true
918
2
DISCUSSION
0
null
null
17,151,076
pmid-1352851|pmid-8900210|pmid-11344258|pmid-9303317|pmid-12819204|pmid-8816488|pmid-8550599|pmid-15169912
This finding is supported by the fact that the complex readily co-purifies despite the fact that neither component when expressed individually in E.coli is particularly stable (data not shown).
null
193
5,499
0
false
null
null
This finding is supported by the fact that the complex readily co-purifies despite the fact that neither component when expressed individually in E.coli is particularly stable (data not shown).
true
true
true
true
true
918