RT Journal Article
SR Electronic
T1 Global lengthening of 3ʹ untranslated regions of mRNAs by alternative cleavage and polyadenylation in cellular senescence
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 033480
DO 10.1101/033480
A1 Miao Han
A1 Guoliang Lv
A1 Hongbo Nie
A1 Ting Shen
A1 Yichi Niu
A1 Xueping Li
A1 Meng Chen
A1 Xia Zheng
A1 Wei Li
A1 Chen Ding
A1 Gang Wei
A1 Jun Gu
A1 Xiao-Li Tian
A1 Yufang Zheng
A1 Xinhua Liu
A1 Jinfeng Hu
A1 Wei Tao
A1 Ting Ni
YR 2015
UL http://biorxiv.org/content/early/2015/12/02/033480.abstract
AB 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 involved in cleavage and the polyadenylation tended to decrease, while those factors showed opposite trend in cancer cells. In summary, we showed, for the first time, that APA is a hidden layer of post-transcriptional gene expression regulation involved in cellular senescence.