蛋白质对RNA甲基化修饰的调控作用与机制:现状与未来展望。
The functions and mechanisms of post-translational modification in protein regulators of RNA methylation: Current status and future perspectives.
发表日期:2023 Sep 08
作者:
Youming Chen, Zuli Jiang, Ying Yang, Chenxing Zhang, Hongyang Liu, Junhu Wan
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
RNA甲基化是一种不改变基因序列的表观遗传修饰,可能对多种生物学过程具有重要作用。RNA甲基化的蛋白质调节因子包括“写入者”、“擦除者”和“读取者”,分别用于沉积、去除和识别甲基化的RNA。RNA甲基化,尤其是N6-甲基腺嘌呤(m6A)、5-甲基胞嘧啶(m5C)、N3-甲基胞嘧啶(m3C)、N1-甲基腺嘌呤(m1A)和N7-甲基鸟苷(m7G),已被提出作为疾病治疗的靶点。尽管RNA甲基化调节蛋白的结构和药理学方面取得了进展,改善了药物发现,但通过各种翻译后修饰(PTM)调节这些蛋白质却受到了很少关注。PTM可以改变蛋白质的结构和功能,影响正常生物学和病理过程的各个方面,包括免疫学、细胞分化、DNA损伤修复和肿瘤等。越来越明显的是RNA甲基化调节因子也受到多种PTM的调控。RNA甲基化调节因子的PTM会导致它们与新的功能团发生共价键连,从而改变其活性和功能。质谱分析已确定了许多对RNA甲基化蛋白质调节因子的PTM。本综述将介绍RNA甲基化蛋白质调节因子的功能和PTM,并总结人类疾病调控模式及其潜在机制的最新进展。版权所有 © 2023. 由Elsevier B.V.出版。
RNA methylation, an epigenetic modification that does not alter gene sequence, may be important to diverse biological processes. Protein regulators of RNA methylation include "writers," "erasers," and "readers," which respectively deposit, remove, and recognize methylated RNA. RNA methylation, particularly N6-methyladenosine (m6A), 5-methylcytosine (m5C), N3-methylcytosine (m3C), N1-methyladenosine (m1A) and N7-methylguanosine (m7G), has been suggested as disease therapeutic targets. Despite advances in the structure and pharmacology of RNA methylation regulators that have improved drug discovery, regulating these proteins by various post-translational modifications (PTMs) has received little attention. PTM modifies protein structure and function, affecting all aspects of normal biology and pathogenesis, including immunology, cell differentiation, DNA damage repair, and tumors. It is becoming evident that RNA methylation regulators are also regulated by diverse PTMs. PTM of RNA methylation regulators induces their covalent linkage to new functional groups, hence modifying their activity and function. Mass spectrometry has identified many PTMs on protein regulators of RNA methylation. In this review, we describe the functions and PTM of protein regulators of RNA methylation and summarize the recent advances in the regulatory mode of human disease and its underlying mechanisms.Copyright © 2023. Published by Elsevier B.V.