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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2018
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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 |
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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 |
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