Zhang Minjie, Lu Zhipeng
Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, China.
Tianjin Key Laboratory of Medical Epigenetics, Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
RNA Biol. 2025 Dec;22(1):1-25. doi: 10.1080/15476286.2024.2442856. Epub 2024 Dec 26.
Transfer RNA (tRNA) is one of the most abundant RNA types in cells, acting as an adaptor to bridge the genetic information in mRNAs with the amino acid sequence in proteins. Both tRNAs and small fragments processed from them play many nonconventional roles in addition to translation. tRNA molecules undergo various types of chemical modifications to ensure the accuracy and efficiency of translation and regulate their diverse functions beyond translation. In this review, we discuss the biogenesis and molecular mechanisms of tRNA modifications, including major tRNA modifications, writer enzymes, and their dynamic regulation. We also summarize the state-of-the-art technologies for measuring tRNA modification, with a particular focus on 2'-O-methylation (Nm), and discuss their limitations and remaining challenges. Finally, we highlight recent discoveries linking dysregulation of tRNA modifications with genetic diseases.
转运RNA（tRNA）是细胞中最丰富的RNA类型之一，作为衔接子，在信使核糖核酸（mRNA）中的遗传信息与蛋白质中的氨基酸序列之间建立联系。tRNA及其加工产生的小片段除了参与翻译过程外，还发挥着许多非常规作用。tRNA分子会经历各种化学修饰，以确保翻译的准确性和效率，并调节其翻译之外的多种功能。在这篇综述中，我们讨论了tRNA修饰的生物合成和分子机制，包括主要的tRNA修饰、书写酶及其动态调控。我们还总结了用于测量tRNA修饰的前沿技术，特别关注2'-O-甲基化（Nm），并讨论了它们的局限性和尚存的挑战。最后，我们重点介绍了近期将tRNA修饰失调与遗传疾病联系起来的发现。
