Protein Stability Buffers the Cost of Translation Attenuation following eIF2α Phosphorylation
Protein Stability Buffers the Cost of Translation Attenuation following eIF2α Phosphorylation
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DOI：
10.1016/j.celrep.2020.108154
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发表时间：
2020-09-15
期刊：
影响因子：
8.8
通讯作者：
Bertolotti, Anne
中科院分区：
文献类型：
--
作者：
Schneider, Kim;Nelson, Geoffrey Michael;Bertolotti, Anne
翻译起始因子eIF2 α的磷酸化是对许多形式的应激的快速和重要的反应，包括内质网中的蛋白质错误折叠应激（ER应激）。据信它会导致蛋白质合成的普遍减少，同时使少数转录本能够翻译。这种蛋白质合成的减少伴随着消耗必需蛋白质的威胁，这种风险被认为是通过其短暂性来减轻的。在这里，我们发现，翻译衰减是不均匀的，与胞质和线粒体核糖体亚基显着下调。这些目标的翻译衰减在翻译恢复后仍然存在。令人惊讶的是，这种情况发生时核糖体蛋白没有可测量的减少。解释这个难题，翻译衰减优先靶向长寿蛋白，这一发现不仅证明了核糖体蛋白，而且在全球范围内观察到。这表明蛋白质稳定性缓冲了翻译衰减的成本，建立了细胞鲁棒性的进化原理。
Phosphorylation of the translation initiation factor eIF2 alpha is a rapid and vital response to many forms of stress, including protein-misfolding stress in the endoplasmic reticulum (ER stress). It is believed to cause a general reduction in protein synthesis while enabling translation of few transcripts. Such a reduction of protein synthesis comes with the threat of depleting essential proteins, a risk thought to be mitigated by its transient nature. Here, we find that translation attenuation is not uniform, with cytosolic and mitochondrial ribosomal subunits being prominently downregulated. Translation attenuation of these targets persists after translation recovery. Surprisingly, this occurs without a measurable decrease in ribosomal proteins. Explaining this conundrum, translation attenuation preferentially targets long-lived proteins, a finding not only demonstrated by ribosomal proteins but also observed at a global level. This shows that protein stability buffers the cost of translational attenuation, establishing an evolutionary principle of cellular robustness.