Cellular stress alters 3′UTR landscape through alternative polyadenylation and isoform-specific degradation

Most eukaryotic genes express alternative polyadenylation (APA) isoforms with different 3′UTR lengths, production of which is influenced by cellular conditions. Here, we show that arsenic stress elicits global shortening of 3′UTRs through preferential usage of proximal polyadenylation sites during s...

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Veröffentlicht in:Nature communications 2018-06, Vol.9 (1), p.1-14, Article 2268
Hauptverfasser: Zheng, Dinghai, Wang, Ruijia, Ding, Qingbao, Wang, Tianying, Xie, Bingning, Wei, Lu, Zhong, Zhaohua, Tian, Bin
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Sprache:eng
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Zusammenfassung:Most eukaryotic genes express alternative polyadenylation (APA) isoforms with different 3′UTR lengths, production of which is influenced by cellular conditions. Here, we show that arsenic stress elicits global shortening of 3′UTRs through preferential usage of proximal polyadenylation sites during stress and enhanced degradation of long 3′UTR isoforms during recovery. We demonstrate that RNA-binding protein TIA1 preferentially interacts with alternative 3′UTR sequences through U-rich motifs, correlating with stress granule association and mRNA decay of long 3′UTR isoforms. By contrast, genes with shortened 3′UTRs due to stress-induced APA can evade mRNA clearance and maintain transcript abundance post stress. Furthermore, we show that stress causes distinct 3′UTR size changes in proliferating and differentiated cells, highlighting its context-specific impacts on the 3′UTR landscape. Together, our data reveal a global, 3′UTR-based mRNA stability control in stressed cells and indicate that APA can function as an adaptive mechanism to preserve mRNAs in response to stress. The function and consequences of alternative polyadenylation (APA) in stressed cells are largely unclear. Here, the authors show that stress-induced mRNA degradation depends on 3′UTR length and that APA-mediated 3′UTR shortening is an adaptive stress response mechanism for selective transcript stabilization.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-04730-7