RT Journal
A1 Chen, Meng
A1 Lyu, Guoliang
A1 Han, Miao
A1 Nie, Hongbo
A1 Shen, Ting
A1 Chen, Wei
A1 Niu, Yichi
A1 Song, Yifan
A1 Li, Xueping
A1 Li, Huan
A1 Chen, Xinyu
A1 Wang, Ziyue
A1 Xia, Zheng
A1 Li, Wei
A1 Tian, Xiao-Li
A1 Ding, Chen
A1 Gu, Jun
A1 Zheng, Yufang
A1 Liu, Xinhua
A1 Hu, Jinfeng
A1 Wei, Gang
A1 Tao, Wei
A1 Ni, Ting
T1 3′ UTR lengthening as a novel mechanism in regulating cellular senescence
JF Genome Research 
JO Genome Research 
YR 2018 
FD March 01 
VO 28 
IS 3 
SP 285 
OP 294 
DO 10.1101/gr.224451.117 
UL http://genome.cshlp.org/content/28/3/285.abstract 
AB Cellular senescence has been viewed as a tumor suppression mechanism and also as a contributor to individual aging. Widespread shortening of 3′ untranslated regions (3′ UTRs) in messenger RNAs (mRNAs) by alternative polyadenylation (APA) has recently been discovered in cancer cells. However, the role of APA in the process of cellular senescence remains elusive. Here, we found that hundreds of genes in senescent cells tended to use distal poly(A) (pA) sites, leading to a global lengthening of 3′ UTRs and reduced gene expression. Genes that harbor longer 3′ UTRs in senescent cells were enriched in senescence-related pathways. Rras2, a member of the Ras superfamily that participates in multiple signal transduction pathways, preferred longer 3′ UTR usage and exhibited decreased expression in senescent cells. Depletion of Rras2 promoted senescence, while rescue of Rras2 reversed senescence-associated phenotypes. Mechanistically, splicing factor TRA2B bound to a core “AGAA” motif located in the alternative 3′ UTR of Rras2, thereby reducing the RRAS2 protein level and causing senescence. Both proximal and distal poly(A) signals showed strong sequence conservation, highlighting the vital role of APA regulation during evolution. Our results revealed APA as a novel mechanism in regulating cellular senescence.