Differential effects of Ydj1 and Sis1 on Hsp70-mediated clearance of stress granules in Saccharomyces cerevisiae.
Differential effects of Ydj1 and Sis1 on Hsp70-mediated clearance of stress granules in Saccharomyces cerevisiae.
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DOI：
10.1261/rna.053116.115
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发表时间：
2015-09
期刊：
影响因子：
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通讯作者：
Parker R
中科院分区：
文献类型：
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作者：
Walters RW;Muhlrad D;Garcia J;Parker R
应激颗粒和P体是真核细胞中保守的非翻译mRNA组装体，它们与一些神经退行性疾病中发现的RNA-蛋白质聚集体有关。在这里，我们研究如何热休克蛋白70/热休克蛋白40蛋白伴侣影响的装配和拆卸的压力颗粒和P-体在酵母中。我们观察到，热休克蛋白70和Ydj 1和Sis 1热休克蛋白40蛋白积累在应力颗粒和缺陷，这些蛋白导致减少拆卸和/或清除应力颗粒。我们观察到单个Hsp 40蛋白对应激颗粒有不同的影响，Ydj 1的缺陷导致应激颗粒在液泡中的积累和应激后翻译的有限恢复，这表明Ydj 1促进应激颗粒的分解以促进翻译。与此相反，Sis 1的缺陷并不影响翻译的恢复，积累细胞质应激颗粒，并显示减少应激颗粒的液泡靶向。这表明了一个新的原则，即替代拆卸机械导致应力颗粒内的组件的不同命运，从而提供了额外的途径来调节它们的组装，组成和功能。此外，热休克蛋白70和热休克蛋白40蛋白在应激颗粒解体的作用耦合这些应激反应结构的组装到细胞的蛋白质稳定状态。
Stress granules and P-bodies are conserved assemblies of nontranslating mRNAs in eukaryotic cells that can be related to RNA–protein aggregates found in some neurodegenerative diseases. Herein, we examine how the Hsp70/Hsp40 protein chaperones affected the assembly and disassembly of stress granules and P-bodies in yeast. We observed that Hsp70 and the Ydj1 and Sis1 Hsp40 proteins accumulated in stress granules and defects in these proteins led to decreases in the disassembly and/or clearance of stress granules. We observed that individual Hsp40 proteins have different effects on stress granules with defects in Ydj1 leading to accumulation of stress granules in the vacuole and limited recovery of translation following stress, which suggests that Ydj1 promotes disassembly of stress granules to promote translation. In contrast, defects in Sis1 did not affect recovery of translation, accumulated cytoplasmic stress granules, and showed reductions in the targeting of stress granules to the vacuole. This demonstrates a new principle whereby alternative disassembly machineries lead to different fates of components within stress granules, thereby providing additional avenues for regulation of their assembly, composition, and function. Moreover, a role for Hsp70 and Hsp40 proteins in stress granule disassembly couples the assembly of these stress responsive structures to the proteostatic state of the cell.