Dec 2, 2015

Global lengthening of 3′ untranslated regions of mRNAs by alternative cleavage and polyadenylation in cellular senescence

BioRxiv : the Preprint Server for Biology
Miao HanTing Ni


Cellular senescence has been viewed as an irreversible cell cycle arrest that acts to prevent cancer. Recent studies discovered widespread shortening of 3′ untranslated regions (3′ UTRs) by alternative cleavage and polyadenylation (APA) in cancer cells. However, the role of APA in the process of cellular senescence remains elusive. We thus applied our published PA-seq method to investigate APA regulation in different passages of mouse embryonic fibroblasts (MEFs) and aortic vascular smooth muscle cells (VSMCs) from rats of different ages. We found that genes in senescent cells tended to use distal poly(A) sites (pAs). An independent RNA-seq analysis gave rise to the same conclusion. Interestingly, the level of expression of genes preferred to use distal pAs in senescent MFEs and VSMCs tended to decrease. More importantly, genes that preferred to use distal pAs in senescent MFEs and VSMCs were enriched in common senescence-related pathways such as ubiquitin-mediated proteolysis and cell cycle. Further, the longer 3′ UTRs of the genes that tended to use distal pAs introduced more conserved binding sites of senescence-related microRNAs (miRNAs) and RNA binding proteins (RBPs). Noteworthy, the expression level of core factors invol...Continue Reading

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Mentioned in this Paper

Biochemical Pathway
Conserved Sequence
Cell Aging
Untranslated Regions
Specimen Type - Fibroblasts
Regulation of Biological Process
Elf4 protein, mouse

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