ULB Center for Diabetes Research, Université Libre de Bruxelles, 1050 Brussels, Belgium.
Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, 1050 Brussels, Belgium.
Int J Mol Sci. 2021 Jan 6;22(2):496. doi: 10.3390/ijms22020496.
The global rise in type 2 diabetes results from a combination of genetic predisposition with environmental assaults that negatively affect insulin action in peripheral tissues and impair pancreatic β-cell function and survival. Nongenetic heritability of metabolic traits may be an important contributor to the diabetes epidemic. Transfer RNAs (tRNAs) are noncoding RNA molecules that play a crucial role in protein synthesis. tRNAs also have noncanonical functions through which they control a variety of biological processes. Genetic and environmental effects on tRNAs have emerged as novel contributors to the pathogenesis of diabetes. Indeed, altered tRNA aminoacylation, modification, and fragmentation are associated with β-cell failure, obesity, and insulin resistance. Moreover, diet-induced tRNA fragments have been linked with intergenerational inheritance of metabolic traits. Here, we provide a comprehensive review of how perturbations in tRNA biology play a role in the pathogenesis of monogenic and type 2 diabetes.
全球 2 型糖尿病发病率的上升是遗传易感性与环境侵袭共同作用的结果，这些因素会对周围组织中胰岛素的作用产生负面影响，并损害胰腺β细胞的功能和存活。代谢特征的非遗传可遗传性可能是糖尿病流行的一个重要因素。转移 RNA（tRNA）是一种非编码 RNA 分子，在蛋白质合成中起着至关重要的作用。tRNA 还具有非规范功能，通过这些功能控制着各种生物学过程。tRNA 上的遗传和环境效应已成为糖尿病发病机制的新贡献者。事实上，tRNA 的氨酰化、修饰和片段化的改变与β细胞衰竭、肥胖和胰岛素抵抗有关。此外，饮食诱导的 tRNA 片段与代谢特征的代际遗传有关。在这里，我们全面回顾了 tRNA 生物学的改变如何在单基因和 2 型糖尿病的发病机制中发挥作用。
