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Genome-wide analysis of pre-mRNA 3' end processing reveals a decisive role of human cleavage factor I in the regulation of 3' UTR length

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Martin Georges, Gruber Andreas, Keller Walter, Zavolan Mihaela,
Project The molecular biology of RNA 3' end processing
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Original article (peer-reviewed)

Journal Cell Reports
Volume (Issue) 1(6)
Page(s) 753 - 763
Title of proceedings Cell Reports
DOI 10.1016/j.celrep.2012.05.003

Open Access

Abstract

Through alternative polyadenylation, human mRNAs acquire longer or shorter 3′ untranslated regions, the latter typically associated with higher transcript stability and increased protein production. To understand the dynamics of polyadenylation site usage, we performed transcriptome-wide mapping of both binding sites of 3′ end processing factors CPSF-160, CPSF-100, CPSF-73, CPSF-30, Fip1, CstF-64, CstF-64τ, CF Im25, CF Im59, and CF Im68 and 3′ end processing sites in HEK293 cells. We found that although binding sites of these factors generally cluster around the poly(A) sites most frequently used in cleavage, CstF-64/CstF-64τ and CFIm proteins have much higher positional specificity compared to CPSF components. Knockdown of CF Im68 induced a systematic use of proximal polyadenylation sites, indicating that changes in relative abundance of a single 3′ end processing factor can modulate the length of 3′ untranslated regions across the transcriptome and suggesting a mechanism behind the previously observed increase in tumor cell invasiveness upon CF Im68 knockdown.
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