Wen Junfei, Zhu Qifan, Liu Yong, Gou Lan-Tao
Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Acta Biochim Biophys Sin (Shanghai). 2024 Nov 21;57(1):33-58. doi: 10.3724/abbs.2024201.
The intricate world of RNA modifications, collectively termed the epitranscriptome, covers over 170 identified modifications and impacts RNA metabolism and, consequently, almost all biological processes. In this review, we focus on the regulatory roles and biological functions of a panel of dominant RNA modifications (including m A, m C, Ψ, ac C, m A, and m G) on three RNA types-mRNA, tRNA, and rRNA-in mammalian development, particularly in the context of reproduction as well as embryonic development. We discuss in detail how those modifications, along with their regulatory proteins, affect RNA processing, structure, localization, stability, and translation efficiency. We also highlight the associations among dysfunctions in RNA modification-related proteins, abnormal modification deposition and various diseases, emphasizing the roles of RNA modifications in critical developmental processes such as stem cell self-renewal and cell fate transition. Elucidating the molecular mechanisms by which RNA modifications influence diverse developmental processes holds promise for developing innovative strategies to manage developmental disorders. Finally, we outline several unexplored areas in the field of RNA modification that warrant further investigation.
RNA修饰的复杂世界，统称为表观转录组，涵盖了170多种已确定的修饰，并影响RNA代谢，进而影响几乎所有的生物学过程。在本综述中，我们重点关注一组主要的RNA修饰（包括m⁶A、m⁵C、Ψ、ac⁴C、m¹A和m⁷G）在哺乳动物发育过程中对三种RNA类型——mRNA、tRNA和rRNA——的调控作用和生物学功能，特别是在生殖以及胚胎发育的背景下。我们详细讨论了这些修饰及其调控蛋白如何影响RNA加工、结构、定位、稳定性和翻译效率。我们还强调了RNA修饰相关蛋白功能障碍、异常修饰沉积与各种疾病之间的关联，强调了RNA修饰在干细胞自我更新和细胞命运转变等关键发育过程中的作用。阐明RNA修饰影响多种发育过程的分子机制，有望为制定管理发育障碍的创新策略提供依据。最后，我们概述了RNA修饰领域中几个有待进一步研究的未探索领域。
