2018
DOI: 10.1101/gr.224451.117
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Abstract: 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 red… Show more

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Cited by 90 publications
(78 citation statements)
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“…We were able to functionally validate these through luciferase reporter assays, highlighting the robustness of our analysis. Consistent with pan-cancer APA analyses, we find enrichment for pathways such as smooth muscle contraction and mRNA 3’-end processing 29,41,43 . However, we also find enrichment for pathways and processes implicated in PDA biology, including protein metabolism, receptor tyrosine kinase signaling and signaling by RHO GTPases.…”
Section: Discussionsupporting
confidence: 81%
See 2 more Smart Citations
“…We were able to functionally validate these through luciferase reporter assays, highlighting the robustness of our analysis. Consistent with pan-cancer APA analyses, we find enrichment for pathways such as smooth muscle contraction and mRNA 3’-end processing 29,41,43 . However, we also find enrichment for pathways and processes implicated in PDA biology, including protein metabolism, receptor tyrosine kinase signaling and signaling by RHO GTPases.…”
Section: Discussionsupporting
confidence: 81%
“…The pattern of 3’-UTR shortening preferentially associated with increased gene expression is consistent with pan-cancer APA analyses and conforms to the expectation that 3’-UTR shortened genes can escape miRNA regulation leading to increased gene expression 30,72,73 . In contrast, 3’-UTR lengthened genes showed a similar number of significantly upregulated (n=42) and significantly downregulated (n=41) genes, consistent with pan-cancer analyses, and most likely reflective of positive and negative regulation by RNA-binding proteins 29,74,75 .…”
Section: Resultssupporting
confidence: 66%
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“…The length of the 3' UTR, and in particular the use of APA sites, is implicated in a number of pathologies including cancer and cell senescence, and in cellular stress response (Chang et al, 2015;Chen et al, 2018a;Mayr and Bartel, 2009). Senescence of cultured primary cells, for example, is a phenomenon linked to NL biology and to the reduction of lamin-B1 (Freund et al, 2014;Shimi et al, 2011).…”
Section: Discussionmentioning
confidence: 99%
“…Since the 3ʹ-UTR contains regulatory regions including microRNA (miRNA) target sites, mRNAs with shortened or lengthened 3ʹ-UTRs may diversify the regulation landscape, for example miRNA binding landscape. In human cancer, 3ʹ-UTR lengthening (3ʹUL) has been associated with cell senescence [2] with implications for tumor-associated processes, such as cell cycle inhibition, DNA damage/repair process, and tumor suppression [3]- [6]. Widespread 3ʹ-UTR shortening (3ʹUS) has been reported for diverse types of human cancer [1].…”
Section: Introductionmentioning
confidence: 99%