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| Status |
Public on Apr 01, 2015 |
| Title |
Regulation of alternative cleavage and polyadenylation by 3’ end processing and splicing factors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Alternative cleavage and polyadenylation (APA) results in mRNA isoforms containing different 3’ untranslated regions (3’UTRs) and/or coding sequences. How core cleavage and polyadenylation (C/P) factors regulate APA is not well understood. Using siRNA knockdown coupled with deep sequencing, we found that several C/P factors can play significant roles in 3’UTR-APA. Whereas Pcf11 and Fip1 enhance usage of proximal poly(A) sites (pAs), CFI-25/68, PABPN1, and PABPC1 promote usage of distal pAs. Strong cis element biases were found for pAs regulated by CFI or Fip1, and the distance between pAs plays an important role in APA regulation. In addition, intronic pAs are substantially regulated by splicing factors, with U1 mostly influencing C/P events in 5’ introns and U2 impacting those in efficiently spliced introns. Furthermore, PABPN1 regulates expression of transcripts with pAs near the transcription start site, a property possibly related to its role in RNA degradation. Finally, we found that groups of APA events regulated by C/P factors are also modulated in cell differentiation and development with distinct trends. Together, our results indicate that the abundance of different C/P factors and splicing factors plays diverse roles in APA, and is relevant to APA regulation in biological conditions.
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| Overall design |
knockdown experiments of 23 C/P factors, 3 splicing factors and U1D in mouse C2C12 myoblast cells
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| Contributor(s) |
Li W, You B, Zheng D, Hoque M, Luo W, Ji Z, Park J, Tian B |
| Citation(s) |
25906188 |
| Submission date |
Oct 02, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Wencheng Li |
| Organization name |
PTC Therapeutics
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| Street address |
100 Corporate Count
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| City |
South Plainfield |
| State/province |
NJ - New Jersey |
| ZIP/Postal code |
07080 |
| Country |
USA |
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| Platforms (3) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (54)
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| Relations |
| BioProject |
PRJNA262911 |
| SRA |
SRP048599 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE62001_mm9.pA.read_counts.add8T.txt.gz |
3.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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