Alternative polyadenylation dependent function of splicing factor SRSF3 contributes to cellular senescence.

ABSTRACT: Down-regulated splicing factor SRSF3 is known to promote cellular senescence, an important biological process in preventing cancer and contributing to individual aging, via its alternative splicing dependent function in human cells. Here we discovered alternative polyadenylation (APA) dependent function of SRSF3 as a novel mechanism explaining SRSF3 downregulation induced cellular senescence. Knockdown of SRSF3 resulted in preference usage of proximal poly(A) sites and thus global shortening of 3' untranslated regions (3' UTRs) of mRNAs. SRSF3-depletion also induced senescence-related phenotypes in both human and mouse cells. These 3' UTR shortened genes were enriched in senescence-associated pathways. Shortened 3' UTRs tended to produce more proteins than the longer ones. Si

SUBMITTER: Shen T 

PROVIDER: S-EPMC6428108 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature