Cellular stress alters 3'UTR landscape through alternative polyadenylation and isoform-specific degradation.
Cellular stress alters 3'UTR landscape through alternative polyadenylation and isoform-specific degradation.
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DOI：
10.1038/s41467-018-04730-7
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发表时间：
2018-06-11
影响因子：
16.6
通讯作者：
Tian B
中科院分区：
文献类型：
--
作者：
Zheng D;Wang R;Ding Q;Wang T;Xie B;Wei L;Zhong Z;Tian B
大多数真核基因表达具有不同3′UTR长度的多聚腺苷酸化（阿帕）异构体，其产生受细胞条件影响。在这里，我们发现砷胁迫通过在胁迫过程中优先使用近端多聚腺苷酸化位点和在恢复过程中增强长3′UTR异构体的降解，从而导致3 ′ UTR的整体缩短。我们证明了RNA结合蛋白TIA1通过富含U的基序优先与替代的3′UTR序列相互作用，与长3′UTR亚型的应激颗粒缔合和mRNA衰变相关。相比之下，由于应激诱导的阿帕而缩短3′ UTR的基因可以逃避mRNA清除并在应激后保持转录丰度。此外，我们表明，压力导致不同的3′UTR大小的变化，在增殖和分化的细胞，突出了其上下文特定的影响3′UTR景观。总之，我们的数据揭示了应激细胞中基于3 'UTR的全局mRNA稳定性控制，并表明阿帕可以作为一种适应机制来保护mRNA以应对应激。选择性多聚腺苷酸化（阿帕）在应激细胞中的功能和后果在很大程度上尚不清楚。在这里，作者表明，胁迫诱导的mRNA降解取决于3′UTR长度，APA介导的3′UTR缩短是选择性转录稳定的适应性胁迫反应机制。
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.
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影响因子：
4.6
作者：
Fontes MM;Guvenek A;Kawaguchi R;Zheng D;Huang A;Ho VM;Chen PB;Liu X;O'Dell TJ;Coppola G;Tian B;Martin KC
通讯作者：
Martin KC
影响因子：
16.6
作者：
Díaz-Muñoz MD;Kiselev VY;Le Novère N;Curk T;Ule J;Turner M
通讯作者：
Turner M
影响因子：
16.2
作者：
Flavell, Steven W.;Kim, Tae-Kyung;Gray, Jesse M.;Harmin, David A.;Hemberg, Martin;Hong, Elizabeth J.;Markenscoff-Papadimitriou, Eirene;Bear, Daniel M.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
7
作者：
Graber JH;Nazeer FI;Yeh PC;Kuehner JN;Borikar S;Hoskinson D;Moore CL
通讯作者：
Moore CL
影响因子：
64.5
作者：
Buchan, J. Ross;Kolaitis, Regina-Maria;Parker, Roy
通讯作者：
Parker, Roy