Abstract：
Heat-shocked cells prioritize the translation of heat shock (HS) mRNAs, but the underlying mechanism is unclear. We report that HS in budding yeast induces the disassembly of the eIF4F complex, where eIF4G and eIF4E assemble into translationally arrested mRNA ribonucleoprotein particles (mRNPs) and HS granules (HSGs), whereas eIF4A promotes HS translation. Using in vitro reconstitution biochemistry, we show that a conformational rearrangement of the thermo-sensing eIF4A-binding domain of eIF4G dissociates eIF4A and promotes the assembly with mRNA into HS-mRNPs, which recruit additional translation factors, including Pab1p and eIF4E, to form multi-component condensates. Using extracts and cellular experiments, we demonstrate that HS-mRNPs and condensates repress the translation of associated mRNA and deplete translation factors that are required for housekeeping translation, whereas HS mRNAs can be efficiently translated by eIF4A. We conclude that the eIF4F complex is a thermo-sensing node that regulates translation during HS.
摘要：
热休克细胞优先翻译热休克（HS）mRNA，但潜在的机制尚不清楚。我们报告说，出芽酵母中的HS诱导eIF4F复合物的分解，其中eIF4G和eIF4E组装成翻译阻滞的mRNA核糖核蛋白颗粒（mRNPs）和HS颗粒（HSGs），而eIF4A促进HS翻译。使用体外重建生物化学，我们表明，eIF4G的热敏eIF4A结合域的构象重排解离eIF4A并促进与mRNA组装成HS-mRNPs，招募额外的翻译因素，包括Pab1p和eIF4E，形成多组分缩合物。使用提取物和细胞实验，我们证明HS-mRNPs和缩合物抑制相关mRNA的翻译，并消耗内务翻译所需的翻译因子，而HSmRNA可以被eIF4A有效翻译。我们得出的结论是，eIF4F复合物是在HS过程中调节平移的热敏节点。
