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

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A gene can express multiple isoforms varying in the 3’ end, a phenomenon called alternative cleavage and polyadenylation, or APA. Previous studies have indicated that most eukaryotic genes display APA and the APA profile changes under different physiological and pathological conditions. However, how APA is regulated in the cell is unclear. Here using gene knockdown and high throughput sequencing we examine how APA is regulated by factors in the machinery responsible for cleavage and polyadenylation as well as factors that play essential roles in splicing. We identify several factors that play significant roles in APA in the last exon, including CFI-25/68, PABPN1, PABPC1, Fip1 and Pcf11. We also elucidate how cleavage and polyadenylation events are regulated in introns and near the transcription start site. We uncover a group of APA events that are highly regulated by core factors as well as in cell differentiation and development. We present an APA code where an APA event in a given cellular context is regulated by a number of parameters, including relative location to the transcription start site, splicing context, distance between competing pAs, surrounding cis elements and concentrations of core cleavage and polyadenylation factors.

Vyšlo v časopise: Systematic Profiling of Poly(A)+ Transcripts Modulated by Core 3’ End Processing and Splicing Factors Reveals Regulatory Rules of Alternative Cleavage and Polyadenylation. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005166
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005166

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