Aging Institute, Department of Medicine, University of Pittsburgh, 100 Technology Drive, Pittsburgh, PA, 15219 USA.
Division of Cardiology, Department of Medicine, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
J Biochem. 2020 Aug 1;168(2):93-102. doi: 10.1093/jb/mvaa061.
The translation of messenger RNA (mRNA) into protein is a multistep process by which genetic information transcribed into an mRNA is decoded to produce a specific polypeptide chain of amino acids. Ribosomes play a central role in translation by coordinately working with various translation regulatory factors and aminoacyl-transfer RNAs. Various stresses attenuate the ribosomal synthesis in the nucleolus as well as the translation rate in the cytosol. To efficiently reallocate cellular energy and resources, mammalian cells are endowed with mechanisms that directly link the suppression of translation-related processes to the activation of stress adaptation programmes. This review focuses on the integrated stress response (ISR) and the nucleolar stress response (NSR) both of which are activated by various stressors and selectively upregulate stress-responsive transcription factors. Emerging findings have delineated the detailed molecular mechanisms of the ISR and NSR and expanded their physiological and pathological significances.
信使 RNA（mRNA）翻译成蛋白质是一个多步骤的过程，其中遗传信息转录成 mRNA 被解码以产生特定的氨基酸多肽链。核糖体通过与各种翻译调节因子和氨酰基转移 RNA 协调工作，在翻译中起着核心作用。各种应激会减弱核仁中的核糖体合成以及细胞质中的翻译速率。为了有效地重新分配细胞能量和资源，哺乳动物细胞具有将与翻译相关的过程的抑制与应激适应程序的激活直接联系起来的机制。这篇综述重点介绍了整合应激反应（ISR）和核仁应激反应（NSR），它们都被各种应激源激活，并选择性地上调应激反应转录因子。新的发现已经描绘了 ISR 和 NSR 的详细分子机制，并扩展了它们的生理和病理意义。
