A comprehensive analysis of 3' end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogeneous ribonucleoprotein C on cleavage and polyadenylation
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 3567622
Author(s) Gruber, Andreas J.; Schmidt, Ralf; Gruber, Andreas R.; Martin, Georges; Ghosh, Souvik; Belmadani, Manuel; Keller, Walter; Zavolan, Mihaela
Author(s) at UniBasel Martin, Georges
Gruber, Andreas
Schmidt, Ralf
Ghosh, Souvik
Belmadani, Manuel
Keller, Walter
Zavolan, Mihaela
Year 2016
Title A comprehensive analysis of 3' end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogeneous ribonucleoprotein C on cleavage and polyadenylation
Journal Genome Research
Volume 26
Number 8
Pages / Article-Number 1145-1159
Abstract Alternative polyadenylation (APA) is a general mechanism of transcript diversification in mammals, which has been recently linked to proliferative states and cancer. Different 3' untranslated region (3' UTR) isoforms interact with different RNA-binding proteins (RBPs), which modify the stability, translation, and subcellular localization of the corresponding transcripts. Although the heterogeneity of pre-mRNA 3' end processing has been established with high-throughput approaches, the mechanisms that underlie systematic changes in 3' UTR lengths remain to be characterized. Through a uniform analysis of a large number of 3' end sequencing data sets, we have uncovered 18 signals, six of which are novel, whose positioning with respect to pre-mRNA cleavage sites indicates a role in pre-mRNA 3' end processing in both mouse and human. With 3' end sequencing we have demonstrated that the heterogeneous ribonucleoprotein C (HNRNPC), which binds the poly(U) motif whose frequency also peaks in the vicinity of polyadenylation (poly(A)) sites, has a genome-wide effect on poly(A) site usage. HNRNPC-regulated 3' UTRs are enriched in ELAV-like RBP 1 (ELAVL1) binding sites and include those of the CD47 gene, which participate in the recently discovered mechanism of 3' UTR-dependent protein localization (UDPL). Our study thus establishes an up-to-date, high-confidence catalog of 3' end processing sites and poly(A) signals, and it uncovers an important role of HNRNPC in regulating 3' end processing. It further suggests that U-rich elements mediate interactions with multiple RBPs that regulate different stages in a transcript's life cycle.
Publisher Cold Spring Harbor Laboratory Press
ISSN/ISBN 1088-9051 ; 1549-5469
edoc-URL http://edoc.unibas.ch/43844/
Full Text on edoc Available
Digital Object Identifier DOI 10.1101/gr.202432.115
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/27382025
ISI-Number WOS:000381733000013
Document type (ISI) Article
 
   

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