Metazoan stress granule assembly is mediated by P-eIF2α-dependent and -independent mechanisms
Metazoan stress granule assembly is mediated by P-eIF2α-dependent and -independent mechanisms
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DOI：
10.1261/rna.1684009
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发表时间：
2009-10-01
期刊：
影响因子：
4.5
通讯作者：
Silver, Pamela A.
中科院分区：
文献类型：
--
作者：
Farny, Natalie G.;Kedersha, Nancy L.;Silver, Pamela A.
应激颗粒（SG）是细胞质体，其中应答性沉默的mRNA被募集用于响应环境应激的分类。我们报告，果蝇细胞形成SGs的反应亚砷酸盐和热休克。果蝇的SGs与哺乳动物的SGs一样，与加工体（PB，mRNA沉默和衰变的位点）不同但相邻，需要多聚核糖体解体，并与多聚核糖体处于动态平衡。我们进一步研究了两个果蝇eIF 2 α激酶，PEK和GCN 2，在调节SG的形成响应于热和砷胁迫的作用。虽然亚砷酸盐诱导的SG依赖于eIF 2 α磷酸化，主要通过PEK，热诱导的SG是磷酸-eIF 2 α-独立的。相比之下，热诱导的SG需要eIF 2 α在哺乳动物细胞中的磷酸化，因为不可磷酸化的eIF 2 α Ser 51 Ala突变型鼠胚胎成纤维细胞即使在严重的热休克后也不形成SG。这些结果表明，哺乳动物进化出了应对热应激的替代机制。
Stress granules (SGs) are cytoplasmic bodies wherein translationally silenced mRNAs are recruited for triage in response to environmental stress. We report that Drosophila cells form SGs in response to arsenite and heat shock. Drosophila SGs, like mammalian SGs, are distinct from but adjacent to processing bodies (PBs, sites of mRNA silencing and decay), require polysome disassembly, and are in dynamic equilibrium with polysomes. We further examine the role of the two Drosophila eIF2 alpha kinases, PEK and GCN2, in regulating SG formation in response to heat and arsenite stress. While arsenite-induced SGs are dependent upon eIF2 alpha phosphorylation, primarily via PEK, heat-induced SGs are phospho-eIF2 alpha-independent. In contrast, heat-induced SGs require eIF2 alpha phosphorylation in mammalian cells, as non-phosphorylatable eIF2 alpha Ser51Ala mutant murine embryonic fibroblasts do not form SGs even after severe heat shock. These results suggest that mammals evolved alternative mechanisms for dealing with thermal stress.