Cargando…

3′ UTR lengthening as a novel mechanism in regulating cellular senescence

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 rol...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Meng, Lyu, Guoliang, Han, Miao, Nie, Hongbo, Shen, Ting, Chen, Wei, Niu, Yichi, Song, Yifan, Li, Xueping, Li, Huan, Chen, Xinyu, Wang, Ziyue, Xia, Zheng, Li, Wei, Tian, Xiao-Li, Ding, Chen, Gu, Jun, Zheng, Yufang, Liu, Xinhua, Hu, Jinfeng, Wei, Gang, Tao, Wei, Ni, Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848608/
https://www.ncbi.nlm.nih.gov/pubmed/29440281
http://dx.doi.org/10.1101/gr.224451.117
_version_ 1783305905570316288
author Chen, Meng
Lyu, Guoliang
Han, Miao
Nie, Hongbo
Shen, Ting
Chen, Wei
Niu, Yichi
Song, Yifan
Li, Xueping
Li, Huan
Chen, Xinyu
Wang, Ziyue
Xia, Zheng
Li, Wei
Tian, Xiao-Li
Ding, Chen
Gu, Jun
Zheng, Yufang
Liu, Xinhua
Hu, Jinfeng
Wei, Gang
Tao, Wei
Ni, Ting
author_facet Chen, Meng
Lyu, Guoliang
Han, Miao
Nie, Hongbo
Shen, Ting
Chen, Wei
Niu, Yichi
Song, Yifan
Li, Xueping
Li, Huan
Chen, Xinyu
Wang, Ziyue
Xia, Zheng
Li, Wei
Tian, Xiao-Li
Ding, Chen
Gu, Jun
Zheng, Yufang
Liu, Xinhua
Hu, Jinfeng
Wei, Gang
Tao, Wei
Ni, Ting
author_sort Chen, Meng
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5848608
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-58486082018-03-20 3′ UTR lengthening as a novel mechanism in regulating cellular senescence Chen, Meng Lyu, Guoliang Han, Miao Nie, Hongbo Shen, Ting Chen, Wei Niu, Yichi Song, Yifan Li, Xueping Li, Huan Chen, Xinyu Wang, Ziyue Xia, Zheng Li, Wei Tian, Xiao-Li Ding, Chen Gu, Jun Zheng, Yufang Liu, Xinhua Hu, Jinfeng Wei, Gang Tao, Wei Ni, Ting Genome Res Research 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. Cold Spring Harbor Laboratory Press 2018-03 /pmc/articles/PMC5848608/ /pubmed/29440281 http://dx.doi.org/10.1101/gr.224451.117 Text en © 2018 Chen et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research
Chen, Meng
Lyu, Guoliang
Han, Miao
Nie, Hongbo
Shen, Ting
Chen, Wei
Niu, Yichi
Song, Yifan
Li, Xueping
Li, Huan
Chen, Xinyu
Wang, Ziyue
Xia, Zheng
Li, Wei
Tian, Xiao-Li
Ding, Chen
Gu, Jun
Zheng, Yufang
Liu, Xinhua
Hu, Jinfeng
Wei, Gang
Tao, Wei
Ni, Ting
3′ UTR lengthening as a novel mechanism in regulating cellular senescence
title 3′ UTR lengthening as a novel mechanism in regulating cellular senescence
title_full 3′ UTR lengthening as a novel mechanism in regulating cellular senescence
title_fullStr 3′ UTR lengthening as a novel mechanism in regulating cellular senescence
title_full_unstemmed 3′ UTR lengthening as a novel mechanism in regulating cellular senescence
title_short 3′ UTR lengthening as a novel mechanism in regulating cellular senescence
title_sort 3′ utr lengthening as a novel mechanism in regulating cellular senescence
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848608/
https://www.ncbi.nlm.nih.gov/pubmed/29440281
http://dx.doi.org/10.1101/gr.224451.117
work_keys_str_mv AT chenmeng 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT lyuguoliang 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT hanmiao 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT niehongbo 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT shenting 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT chenwei 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT niuyichi 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT songyifan 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT lixueping 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT lihuan 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT chenxinyu 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT wangziyue 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT xiazheng 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT liwei 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT tianxiaoli 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT dingchen 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT gujun 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT zhengyufang 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT liuxinhua 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT hujinfeng 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT weigang 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT taowei 3utrlengtheningasanovelmechanisminregulatingcellularsenescence
AT niting 3utrlengtheningasanovelmechanisminregulatingcellularsenescence