TY  - JOUR
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
Y1  - 2018/03/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 285 
EP  - 294 
DO  - 10.1101/gr.224451.117 
VL  - 28 
IS  - 3 
UR  - http://genome.cshlp.org/content/28/3/285.abstract 
N2  - 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. 
ER  -