Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells
Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells
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DOI：
10.1242/bio.046391
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发表时间：
2020-07-01
期刊：
影响因子：
2.4
通讯作者：
Alberti, Simon
中科院分区：
文献类型：
--
作者：
Nuske, Elisabeth;Marini, Guendalina;Alberti, Simon
处于饥饿状态的细胞必须调整新陈代谢以保存能量并保护自己。蛋白质合成是主要的能量消耗过程之一，因此必须严格控制。关于饥饿细胞如何调节蛋白质合成过程的许多机制细节仍然是未知的。在这里，我们报告说，必不可少的翻译起始因子eIF2B在饥饿芽殖酵母细胞中形成细丝。我们证明，饥饿诱导的酸化的胞质溶胶，这是由质子从细胞外环境的流入所引起的触发。我们表明，eIF 2B的细丝组装对于快速有效的翻译下调是必要的。重要的是，这种机制不需要激酶Gcn 2。此外，位点特异性变体的分析表明，eIF2B组装导致酶失活的细丝，其促进细胞的应激存活和从饥饿中快速恢复。我们提出，通过丝组装的翻译调节是一种有效的机制，使酵母细胞适应波动的环境。
Cells exposed to starvation have to adjust their metabolism to conserve energy and protect themselves. Protein synthesis is one of the major energy-consuming processes and as such has to be tightly controlled. Many mechanistic details about how starved cells regulate the process of protein synthesis are still unknown. Here, we report that the essential translation initiation factor eIF2B forms filaments in starved budding yeast cells. We demonstrate that filamentation is triggered by starvation-induced acidification of the cytosol, which is caused by an influx of protons from the extracellular environment. We show that filament assembly by eIF2B is necessary for rapid and efficient downregulation of translation. Importantly, this mechanism does not require the kinase Gcn2. Furthermore, analysis of site -specific variants suggests that eIF2B assembly results in enzymatically inactive filaments that promote stress survival and fast recovery of cells from starvation. We propose that translation regulation through filament assembly is an efficient mechanism that allows yeast cells to adapt to fluctuating environments.