Paralogous translation factors target distinct mRNAs to differentially regulate tolerance to oxidative stress in yeast.
Paralogous translation factors target distinct mRNAs to differentially regulate tolerance to oxidative stress in yeast.
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DOI：
10.1093/nar/gkad568
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发表时间：
2023-09-08
影响因子：
14.9
通讯作者：
Grant, Chris M.
中科院分区：
文献类型：
--
作者：
Cunningham, Joanne;Sfakianos, Aristeidis P.;Kritsiligkou, Paraskevi;Kershaw, Christopher J.;Whitmarsh, Alan J.;Hubbard, Simon J.;Ashe, Mark P.;Grant, Chris M.
翻译起始因子4G（translation initiation factor 4G，eIF4G）是eIF4F复合物的一个组成部分，是大多数真核生物mRNA翻译起始的关键。许多eIF4G异构体已被描述在不同的真核生物，但我们目前有一个贫穷的了解他们的功能作用，以及他们是否调节翻译的mRNA特异性的方式。酵母酿酒酵母表达两种eIF 4G亚型eIF 4G1和eIF 4G2，之前认为这两种亚型在功能上是冗余的，任何表型差异都是由于eIF 4G表达水平的改变而产生的。使用表达eIF4G1或eIF4G2作为唯一eIF4G亚型的同源菌株，其表达水平与总eIF4G相当，我们表明eIF4G1是介导氧化应激翻译反应所必需的。eIF4G1结合mRNA帽，并在氧化应激条件下与积极翻译的核糖体保持联系，我们使用定量蛋白质组学显示，eIF4G1促进氧化应激特异性蛋白质组的变化。eIF4G1而不是eIF4G2结合Slf1 LARP蛋白，该蛋白似乎介导eIF4G1依赖的对氧化应激的翻译应答。我们显示了eIF4G在人类细胞中类似的亚型特异性作用，这表明多个eIF4G亚型的趋同进化提供了显着的优势，特别是在翻译必须在应激条件下继续的情况下。
Translation initiation factor 4G (eIF4G) is an integral component of the eIF4F complex which is key to translation initiation for most eukaryotic mRNAs. Many eIF4G isoforms have been described in diverse eukaryotic organisms but we currently have a poor understanding of their functional roles and whether they regulate translation in an mRNA specific manner. The yeast Saccharomyces cerevisiae expresses two eIF4G isoforms, eIF4G1 and eIF4G2, that have previously been considered as functionally redundant with any phenotypic differences arising due to alteration in eIF4G expression levels. Using homogenic strains that express eIF4G1 or eIF4G2 as the sole eIF4G isoforms at comparable expression levels to total eIF4G, we show that eIF4G1 is specifically required to mediate the translational response to oxidative stress. eIF4G1 binds the mRNA cap and remains associated with actively translating ribosomes during oxidative stress conditions and we use quantitative proteomics to show that eIF4G1 promotes oxidative stress-specific proteome changes. eIF4G1, but not eIF4G2, binds the Slf1 LARP protein which appears to mediate the eIF4G1-dependent translational response to oxidative stress. We show similar isoform specific roles for eIF4G in human cells suggesting convergent evolution of multiple eIF4G isoforms offers significant advantages especially where translation must continue under stress conditions.
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