Cellular stress induces cytoplasmic RNA granules in fission yeast

Cellular stress induces cytoplasmic RNA granules in fission yeast
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DOI:
10.1261/rna.2268111
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发表时间:
2011-01-01
期刊:
RNA
影响因子:
4.5
通讯作者:
Sunnerhagen, Per
Sunnerhagen, Per
中科院分区:
生物学3区
文献类型:
--
作者:
Nilsson, Daniel;Sunnerhagen, Per

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严重的压力会导致植物和动物细胞形成含有RNA和蛋白质的大细胞质颗粒。在这里,我们证明了存在应力诱导的胞质RNA颗粒粟酒裂殖酵母。在分裂酵母RNA颗粒中发现了哺乳动物加工体和应激颗粒的几种已知蛋白质组分的同源物。与哺乳动物细胞相反,poly(A)-binding protein(Pabp)与decapping protein共定位于应激诱导的颗粒中。在葡萄糖剥夺后,蛋白激酶A(PKA)是Pabp阳性颗粒积累和翻译下调所必需的。这是PKA在RNA颗粒形成中的作用的首次证明。在哺乳动物中,翻译起始蛋白eIF 2 α是形成含有多聚腺苷酸结合蛋白的颗粒的关键调节因子。In S.粟酒裂殖酵母,非磷酸化eIF 2 α不阻断,但延迟颗粒形成和随后的清除后,暴露于高渗透。在S.粟酒裂殖酵母似乎调节应激诱导的颗粒:pka 1突变体完全精通高渗休克后形成颗粒;相反,eIF 2 α不影响葡萄糖饥饿中的颗粒形成。此外,我们证明了钙扰动和RNA颗粒之间的Pka 1依赖性联系,这在任何生物体中都没有被描述过。
Severe stress causes plant and animal cells to form large cytoplasmic granules containing RNA and proteins. Here, we demonstrate the existence of stress-induced cytoplasmic RNA granules in Schizosaccharomyces pombe. Homologs to several known protein components of mammalian processing bodies and stress granules are found in fission yeast RNA granules. In contrast to mammalian cells, poly(A)-binding protein (Pabp) colocalizes in stress-induced granules with decapping protein. After glucose deprivation, protein kinase A (PKA) is required for accumulation of Pabp-positive granules and translational down-regulation. This is the first demonstration of a role for PKA in RNA granule formation. In mammals, the translation initiation protein eIF2 alpha is a key regulator of formation of granules containing poly(A)-binding protein. In S. pombe, nonphosphorylatable eIF2 alpha does not block but delays granule formation and subsequent clearance after exposure to hyperosmosis. At least two separate pathways in S. pombe appear to regulate stress-induced granules: pka1 mutants are fully proficient to form granules after hyperosmotic shock; conversely, eIF2 alpha does not affect granule formation in glucose starvation. Further, we demonstrate a Pka1-dependent link between calcium perturbation and RNA granules, which has not been described earlier in any organism.