Journal
CELL REPORTS
Volume 1, Issue 6, Pages 753-763Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2012.05.003
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Funding
- University of Basel
- Louis-Jeantet Foundation for Medicine
- Swiss National Science Foundation [31003A_133145]
- Swiss National Science Foundation (SNF) [31003A_133145] Funding Source: Swiss National Science Foundation (SNF)
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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-64 tau, CF I(m)25, CF I(m)59, and CF I(m)68 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-64 tau and CFIm proteins have much higher positional specificity compared to CPSF components. Knockdown of CF I(m)68 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 I(m)68 knockdown.
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