Department of Cell and Molecular Biology, Lundberg Laboratory, University of Gothenburg, S-405 30 Göteborg, Sweden.
RNA. 2011 Jan;17(1):120-33. doi: 10.1261/rna.2268111. Epub 2010 Nov 22.
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 eIF2α is a key regulator of formation of granules containing poly(A)-binding protein. In S. pombe, nonphosphorylatable eIF2α 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, eIF2α 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.
严重的应激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,我们证明了应激诱导的裂殖酵母细胞质 RNA 颗粒的存在。在裂殖酵母的 RNA 颗粒中发现了几种与哺乳动物加工体和应激颗粒的已知蛋白成分同源的蛋白。与哺乳动物细胞不同的是,poly(A)结合蛋白(Pabp)与脱帽蛋白一起定位于应激诱导的颗粒中。葡萄糖剥夺后,蛋白激酶 A(PKA)对于 Pabp 阳性颗粒的积累和翻译下调是必需的。这是 PKA 在 RNA 颗粒形成中作用的首次证明。在哺乳动物中,翻译起始蛋白 eIF2α 是形成含有 poly(A)结合蛋白的颗粒的关键调节剂。在裂殖酵母中,非磷酸化的 eIF2α 不会阻止但会延迟颗粒的形成,并在暴露于高渗后随后清除。裂殖酵母中似乎存在至少两种独立的途径来调节应激诱导的颗粒:pka1 突变体在高渗冲击后完全能够形成颗粒;相反,eIF2α 不会影响葡萄糖饥饿时颗粒的形成。此外,我们证明了钙扰动和 RNA 颗粒之间的 Pka1 依赖性联系,这在任何生物体中以前都没有描述过。