Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA.
Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA.
Mol Cell. 2024 Jun 6;84(11):2135-2151.e7. doi: 10.1016/j.molcel.2024.04.016.
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.
在应对压力时，真核生物通过磷酸化 eIF2α 激活整合应激反应（ISR），以促进生存相关效应基因的翻译，如酵母中的 GCN4。与 ISR 互补的是雷帕霉素靶蛋白（TOR）通路，它调节 eIF4E 的功能。在这里，我们在酿酒酵母中探测没有 eIF4E 的翻译控制。有趣的是，我们发现 eIF4E 的缺失导致 GCN4 翻译去阻遏。此外，我们发现 GCN4 翻译的去阻遏既不伴随着 eIF2α 磷酸化，也不伴随着起始三元复合物（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阻遏，这可能涉及由于 eIF4A 的局部浓度增加，小核糖体亚基更快地扫描。总的来说，我们的发现表明，eIF4F 成分的相对水平是核糖体动力学的关键，可能在基因表达的翻译控制中发挥重要作用。
