Insights into the role of yeast eIF2A in IRES-mediated translation.

Insights into the role of yeast eIF2A in IRES-mediated translation.
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DOI:
10.1371/journal.pone.0024492
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Merrick WC
Merrick WC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Reineke LC;Cao Y;Baus D;Hossain NM;Merrick WC

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真核起始因子2A是在正常细胞条件下负调节IRES介导的翻译的单一多肽。我们已经发现,在模拟酵母酿酒酵母(Saccharomycescerevisiae)中二次生长转变的条件下,在6%乙醇胁迫(或37°C热休克)期间,eIF 2A(由YGR 054 w编码)丰度在mRNA和蛋白质水平上都降低。此外,eIF 2A蛋白在乙醇强制降解过程中发生后修饰。与乙醇和热激胁迫不同,H2 O2和山梨醇处理诱导eIF 2A mRNA的丢失,但不诱导蛋白质的丢失,并且没有蛋白质修饰。为了研究eIF 2A功能的机制,我们采用免疫沉淀-质谱法,并确定了eIF 2A和eEF 1A之间的相互作用。在乙醇胁迫期间,eIF 2A和eEF 1A之间的相互作用增加,这与URE 2 IRES元件的IRES介导的翻译增加相关。这些数据表明,eIF 2A作为一个开关,以调节IRES介导的翻译,和eEF 1A可能是一个重要的介导的翻译激活在乙醇胁迫。
Eukaryotic initiation factor 2A is a single polypeptide that acts to negatively regulate IRES-mediated translation during normal cellular conditions. We have found that eIF2A (encoded by YGR054w) abundance is reduced at both the mRNA and protein level during 6% ethanol stress (or 37°C heat shock) under conditions that mimic the diauxic shift in the yeast Saccharomyces cerevisiae. Furthermore, eIF2A protein is posttranslationally modified during ethanol stress. Unlike ethanol and heat shock stress, H2O2 and sorbitol treatment induce the loss of eIF2A mRNA, but not protein and without protein modification. To investigate the mechanism of eIF2A function we employed immunoprecipitation-mass spectrometry and identified an interaction between eIF2A and eEF1A. The interaction between eIF2A and eEF1A increases during ethanol stress, which correlates with an increase in IRES-mediated translation from the URE2 IRES element. These data suggest that eIF2A acts as a switch to regulate IRES-mediated translation, and eEF1A may be an important mediator of translational activation during ethanol stress.
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