PDF(Pubmed)
Abstract：
In response to stress, eukaryotes activate the integrated stress response (ISR) via phosphorylation of eIF2α to promote the translation of pro-survival effector genes, such as GCN4 in yeast. Complementing the ISR is the target of rapamycin (TOR) pathway, which regulates eIF4E function. Here, we probe translational control in the absence of eIF4E in Saccharomyces cerevisiae. Intriguingly, we find that loss of eIF4E leads to de-repression of GCN4 translation. In addition, we find that de-repression of GCN4 translation is accompanied by neither eIF2α phosphorylation nor reduction in initiator ternary complex (TC). Our data suggest that when eIF4E levels are depleted, GCN4 translation is de-repressed via a unique mechanism that may involve faster scanning by the small ribosome subunit due to increased local concentration of eIF4A. Overall, our findings suggest that relative levels of eIF4F components are key to ribosome dynamics and may play important roles in translational control of gene expression.
摘要：
为了应对压力，真核生物通过磷酸化eIF2α激活整合应激反应（ISR），以促进促存活效应基因的翻译，如酵母中的GCN4。补充ISR是雷帕霉素（TOR）通路的靶标，它规范了eIF4E功能。这里,我们在酿酒酵母中没有eIF4E的情况下探索翻译控制。有趣的是，我们发现eIF4E的丢失导致GCN4翻译的去抑制。此外,我们发现GCN4翻译的去抑制既不伴随eIF2α磷酸化也不伴随引发剂三元复合物（TC）的减少。我们的数据表明，当eIF4E水平耗尽时，GCN4翻译通过一种独特的机制去抑制,该机制可能涉及小核糖体亚基由于eIF4A的局部浓度增加而进行更快的扫描。总的来说,我们的研究结果表明,eIF4F成分的相对水平是核糖体动力学的关键,并可能在基因表达的翻译控制中发挥重要作用.
