Cellular Stress Alters 3'UTR Landscape Through Alternative Polyadenylation and Isoform-specific Degradation

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Jun 13

PMID 29891946

Citations 63

Authors

Dinghai Zheng

Ruijia Wang

Qingbao Ding

Tianying Wang

Bingning Xie

Lu Wei

Zhaohua Zhong

Bin Tian

Affiliations

Soon will be listed here.

Abstract

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.

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