Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA; email:
Graduate Field of Biomedical and Biological Sciences, Cornell University, Ithaca, New York 14853, USA.
Annu Rev Nutr. 2020 Sep 23;40:51-75. doi: 10.1146/annurev-nutr-120919-041411. Epub 2020 Jul 6.
The emergence of genome-wide analyses to interrogate cellular DNA, RNA, and protein content has revolutionized the study of control networks that mediate cellular homeostasis. mRNA translation represents the last step of genetic flow and primarily defines the proteome. Translational regulation is thus critical for gene expression, in particular under nutrient excess or deficiency. Until recently, it was unclear how the global effects of translational control are orchestrated by nutrient signaling pathways. An emerging concept of translational reprogramming addresses how to maintain the expression of specific proteins during nutrient stress by translation of selective mRNAs. In this review, we describe recent advances in our understanding of translational control principles; nutrient-sensing mechanisms; and their dysregulation in human diseases such as diabetes, cancer, and aging. The mechanistic understanding of translational regulation in response to different nutrient conditions may help identify potential dietary and therapeutic targets to improve human health.
基因组分析技术的出现,使人们可以研究细胞内的 DNA、RNA 和蛋白质含量,从而彻底改变了调控细胞内环境稳定的控制网络的研究。mRNA 翻译是遗传信息流的最后一步,主要决定蛋白质组。因此,翻译调控对于基因表达至关重要,特别是在营养过剩或不足的情况下。直到最近,人们还不清楚营养信号通路如何协调翻译控制的全局效应。翻译重编程的一个新兴概念解决了如何在营养胁迫下通过选择性 mRNA 的翻译来维持特定蛋白质的表达的问题。在这篇综述中,我们描述了对翻译控制原理、营养感应机制及其在糖尿病、癌症和衰老等人类疾病中的失调的理解的最新进展。对不同营养条件下翻译调控的机制理解可能有助于确定潜在的饮食和治疗靶点,以改善人类健康。