eIF5A promotes translation elongation, polysome disassembly and stress granule assembly.
eIF5A promotes translation elongation, polysome disassembly and stress granule assembly.
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DOI：
10.1371/journal.pone.0009942
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发表时间：
2010-04-01
期刊：
影响因子：
3.7
通讯作者：
Anderson P
中科院分区：
文献类型：
--
作者：
Li CH;Ohn T;Ivanov P;Tisdale S;Anderson P
应激颗粒(SGS)是暴露在环境应激下的细胞中未翻译的mRNAs积累的细胞质焦点。我们已经确定鸟氨酸脱羧酶(ODC)和eIF5A是亚砷酸盐诱导的SG组装所需的蛋白质。鸟氨酸脱羧酶是合成多胺所必需的酶，eIF5A是多胺(亚硫氨酸)修饰的翻译因子。敲除脱氧亚硫氨酸合成酶(DHS)或用脱氧亚硫氨酸合成酶抑制剂(GC7)处理可阻止eIF5A的亚硫氨酸修饰以及亚砷酸盐诱导的多聚体解体和应激颗粒组装。时间进程分析表明，这是由于缺乏亚硫氨酸-eIF5A的细胞中应激诱导的核糖体流失放缓。虽然eIF5A在正常情况下只对蛋白质合成产生轻微影响，但它是压力诱导的翻译抑制快速启动所必需的。我们的结果表明，在恶劣的环境条件下，亚精氨酸-eIF5A促进的翻译延长促进了亚砷酸盐诱导的多聚体的分解和应激颗粒的组装。
Stress granules (SGs) are cytoplasmic foci at which untranslated mRNAs accumulate in cells exposed to environmental stress. We have identified ornithine decarboxylase (ODC), an enzyme required for polyamine synthesis, and eIF5A, a polyamine (hypusine)-modified translation factor, as proteins required for arsenite-induced SG assembly. Knockdown of deoxyhypusine synthase (DHS) or treatment with a deoxyhypusine synthase inhibitor (GC7) prevents hypusine modification of eIF5A as well as arsenite-induced polysome disassembly and stress granule assembly. Time-course analysis reveals that this is due to a slowing of stress-induced ribosome run-off in cells lacking hypusine-eIF5A. Whereas eIF5A only marginally affects protein synthesis under normal conditions, it is required for the rapid onset of stress-induced translational repression. Our results reveal that hypusine-eIF5A-facilitated translation elongation promotes arsenite-induced polysome disassembly and stress granule assembly in cells subjected to adverse environmental conditions.
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影响因子：
64.8
作者：
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发表时间：
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