Stress granules are dispensable for mRNA stabilization during cellular stress.
Stress granules are dispensable for mRNA stabilization during cellular stress.
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DOI：
10.1093/nar/gku1275
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发表时间：
2015-02-27
影响因子：
14.9
通讯作者：
Hüttelmaier S
中科院分区：
文献类型：
--
作者：
Bley N;Lederer M;Pfalz B;Reinke C;Fuchs T;Glaß M;Möller B;Hüttelmaier S
在细胞应激期间，蛋白质合成严重减少，大量mRNA被募集到应激颗粒（SG）。以前，我们表明，SG募集的IGF 2 mRNA结合蛋白1（IGF 2BP 1）干扰细胞应激过程中的靶mRNA降解。这是否需要组建SG仍然是难以捉摸的。在这里，我们证明了可见的SG的持续抑制需要TIA 1，TIAR和G3 BP 1的伴随敲低。然而，FRAP和光转换研究表明，这些蛋白质只是短暂地与SG相关联。这表明TIA蛋白和G3 BP 1通过不断补充mRNP来促进SG形成，而不是形成用于mRNP募集的刚性支架。与此相反，RNA结合蛋白如IGF 2BP 1或HUR，其对于SG组装是不稳定的，与SG稳定相关，并且IGF 2BP 1/HUR-G3 BP 1关联在应激期间增加。IGF 2BP 1的耗竭增强了靶mRNA的降解，而不管是否抑制SG形成，而当SG形成受损时，大量mRNA的周转率仍不受影响。总之，这些发现表明，在细胞应激期间mRNA的稳定化是通过形成稳定的mRNP来促进的，所述mRNP通过TIA蛋白和/或G3 BP 1募集到SG。然而，重要的是，mRNP聚集成可见的SG对于防止mRNA降解是不利的。
During cellular stress, protein synthesis is severely reduced and bulk mRNA is recruited to stress granules (SGs). Previously, we showed that the SG-recruited IGF2 mRNA-binding protein 1 (IGF2BP1) interferes with target mRNA degradation during cellular stress. Whether this requires the formation of SGs remained elusive. Here, we demonstrate that the sustained inhibition of visible SGs requires the concomitant knockdown of TIA1, TIAR and G3BP1. FRAP and photo-conversion studies, however, indicate that these proteins only transiently associate with SGs. This suggests that instead of forming a rigid scaffold for mRNP recruitment, TIA proteins and G3BP1 promote SG-formation by constantly replenishing mRNPs. In contrast, RNA-binding proteins like IGF2BP1 or HUR, which are dispensable for SG-assembly, are stably associated with SGs and the IGF2BP1/HUR-G3BP1 association is increased during stress. The depletion of IGF2BP1 enhances the degradation of target mRNAs irrespective of inhibiting SG-formation, whereas the turnover of bulk mRNA remains unaffected when SG-formation is impaired. Together these findings indicate that the stabilization of mRNAs during cellular stress is facilitated by the formation of stable mRNPs, which are recruited to SGs by TIA proteins and/or G3BP1. Importantly, however, the aggregation of mRNPs to visible SGs is dispensable for preventing mRNA degradation.
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多核体解离时过量的自由mRNA是蛋白质多聚化的支架，形成应激颗粒。
影响因子：
14.9
作者：
Bounedjah O;Desforges B;Wu TD;Pioche-Durieu C;Marco S;Hamon L;Curmi PA;Guerquin-Kern JL;Piétrement O;Pastré D
通讯作者：
Pastré D
影响因子：
7.8
作者：
Buchan, J. Ross;Muhlrad, Denise;Parker, Roy
通讯作者：
Parker, Roy
影响因子：
16
作者：
Eisinger-Mathason, T. S. Karin;Andrade, Josefa;Groehler, Angela L.;Clark, David E.;Muratore-Schroeder, Tara L.;Pasic, Lejla;Smith, Jeffrey A.;Shabanowitz, Jeffrey;Hunt, Donald F.;Macara, Ian G.;Lannigan, Deborah A.
通讯作者：
Lannigan, Deborah A.
影响因子：
2.9
作者：
Ash, Peter E. A.;Vanderweyde, Tara E.;Youmans, Katherine L.;Apicco, Daniel J.;Wolozin, Benjamin
通讯作者：
Wolozin, Benjamin
DOI：
10.1083/jcb.201302044
发表时间：
2013-04-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Li YR;King OD;Shorter J;Gitler AD
通讯作者：
Gitler AD