PDF(Pubmed)
Abstract：
Upon oxidative stress, mammalian cells rapidly reprogram their translation. This is accompanied by the formation of stress granules (SGs), cytoplasmic ribonucleoprotein condensates containing untranslated mRNA molecules, RNA-binding proteins, 40S ribosomal subunits, and a set of translation initiation factors. Here we show that arsenite-induced stress causes a dramatic increase in the stop-codon readthrough rate and significantly elevates translation reinitiation levels on uORF-containing and bicistronic mRNAs. We also report the recruitment of translation termination factors eRF1 and eRF3, as well as ribosome recycling and translation reinitiation factors ABCE1, eIF2D, MCT-1, and DENR to SGs upon arsenite treatment. Localization of these factors to SGs may contribute to a rapid resumption of mRNA translation after stress relief and SG disassembly. It may also suggest the presence of post-termination, recycling, or reinitiation complexes in SGs. This new layer of translational control under stress conditions, relying on the altered spatial distribution of translation factors between cellular compartments, is discussed.
摘要：
在氧化应激时，哺乳动物细胞迅速重新编程它们的翻译。这伴随着应力颗粒（SGs）的形成，含有非翻译mRNA分子的细胞质核糖核蛋白缩合物，RNA结合蛋白，40S核糖体亚基，和一组翻译启动因素。在这里，我们表明，亚砷酸盐诱导的应激导致终止密码子连读率的显着增加，并显着提高含uORF和双顺反子mRNA的翻译重新起始水平。我们还报告了翻译终止因子eRF1和eRF3的招募，以及核糖体再循环和翻译重新起始因子ABCE1，eIF2D，亚砷酸盐处理后的MCT-1和SGs的DENR。这些因子在SGs中的定位可能有助于缓解压力和SG分解后mRNA翻译的快速恢复。这也可能表明存在终止后，回收,或SGs中的重新起始复合物。在应力条件下的这种新的平移控制层，依赖于细胞区室之间翻译因子的空间分布的改变，正在讨论。
