Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Diabetes Obes Metab. 2018 Sep;20 Suppl 2:20-27. doi: 10.1111/dom.13405.
Efficient and accurate protein translation is essential to producing insulin in pancreatic β-cells. Transfer RNA (tRNA) is known as the key component of the protein translational machinery. Interestingly, tRNA contains a wide variety of chemical modifications, which are posttranscriptionally catalysed by tRNA modifying enzymes. Recent advances in genome-sequencing technology have unveiled a number of genetic variations that are associated with the development of type 2 diabetes (T2D). Some of these mutations are located in the genes of tRNA modifying enzymes. Using cellular and animal models, it has been showed that dysregulation of tRNA modification impairs protein translation in pancreatic β-cells and leads to aberrant insulin production. In this review, we discuss the recent findings in the molecular functions of tRNA modifications and their involvement in the development of T2D.
高效准确的蛋白质翻译对于在胰腺β细胞中产生胰岛素至关重要。转移 RNA(tRNA)是蛋白质翻译机制的关键组成部分。有趣的是,tRNA 含有多种化学修饰,这些修饰是由 tRNA 修饰酶转录后催化的。最近基因组测序技术的进步揭示了一些与 2 型糖尿病(T2D)发展相关的遗传变异。其中一些突变位于 tRNA 修饰酶的基因中。使用细胞和动物模型,已经表明 tRNA 修饰的失调会损害胰腺β细胞中的蛋白质翻译,并导致异常的胰岛素产生。在这篇综述中,我们讨论了 tRNA 修饰的分子功能及其在 T2D 发展中的作用的最新发现。