Systematic Profiling of Poly(A)+ Transcripts Modulated by Core 3’ End Processing and Splicing Factors Reveals Regulatory Rules of Alternative Cleavage and Polyadenylation

• DOI: 10.1371/journal.pgen.1005166
• Publication Date: 2015-04-23T20:22:43Z
• Authors: Wencheng Li; Bei You; Mainul Hoque; Dinghai Zheng; Wenting Luo; Zhe Ji; Ji Yeon Park; Samuel I. Gunderson; Auinash Kalsotra; James L. Manley; Bin Tian
• Keywords: Post-transcriptional modification

Alternative cleavage and polyadenylation (APA) results in mRNA isoforms containing different 3' untranslated regions (3'UTRs) and/or coding sequences. How core cleavage/polyadenylation (C/P) factors regulate APA is not well understood. Using siRNA knockdown coupled with deep sequencing, we found that several C/P can play significant roles 3'UTR-APA. Whereas Pcf11 Fip1 enhance usage of proximal poly(A) sites (pAs), CFI-25/68, PABPN1 PABPC1 promote distal pAs. Strong cis element biases were for pAs regulated by CFI-25/68 or Fip1, the distance between plays an important role regulation. In addition, intronic are substantially splicing factors, U1 mostly inhibiting events introns near 5' end gene U2 suppressing those features efficient splicing. Furthermore, inhibits expression transcripts transcription start site (TSS), a property possibly related to its RNA degradation. Finally, groups also modulated cell differentiation development distinct trends. Together, our support code where event given cellular context number parameters, including relative location TSS, context, competing pAs, surrounding elements concentrations factors.