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健康与疾病中的RNA修饰

RNA Modifications in Health and Disease.

作者信息

Li Shiqi, Luo Ping, Fan Junli, Li Yirong, Tu Jiancheng, Long Xinghua

机构信息

Department of Laboratory Medicine Zhongnan Hospital of Wuhan University Wuhan China.

Department of Clinical Laboratory Medicine Xijing Hospital Fourth Military Medical University (Air Force Medical University) Xi'an China.

出版信息

MedComm (2020). 2025 Sep 3;6(9):e70341. doi: 10.1002/mco2.70341. eCollection 2025 Sep.

Abstract

RNA modifications, including N6-methyladenosine (m6A), 5-methylcytosine, and pseudouridine, serve as pivotal regulators of gene expression with significant implications for human health and disease. These dynamic modifications influence RNA stability, splicing, translation, and interactions, thereby orchestrating critical biological processes such as embryonic development, immune response, and cellular homeostasis. Dysregulation of RNA modifications is closely associated with a variety of pathologies. This review systematically synthesizes recent advances in understanding how dynamic RNA modifications orchestrate health and disease. We critically review the m6A modifications, the most abundant RNA methylation, its association with diseases, and regulations by post translation. We evaluate three interconnected themes: disease mechanisms, where dysregulated m6A drives oncogenesis (e.g., METTL3-mediated hypermethylation in breast cancer) and contributes to neuropsychiatric/cardiovascular disorders; homeostatic functions, spanning embryogenesis (maternal-to-zygotic transition), tissue regeneration (YTHDF1 in muscle), and immune regulation; therapeutic frontiers, including enzyme-targeting strategies (FTO inhibitors, METTL3 stabilizers) and diagnostic approaches. Our analysis reveals that context-dependent RNA modification networks operate as biological "switches" whose dysregulation creates pathogenic cascades. We further propose a novel framework for targeting these networks using multiomics integration. This review establishes RNA modifications as central targets for precision medicine, while highlighting critical challenges in clinical translation that demand interdisciplinary collaboration.

摘要

RNA修饰,包括N6-甲基腺苷(m6A)、5-甲基胞嘧啶和假尿苷,作为基因表达的关键调节因子,对人类健康和疾病具有重要意义。这些动态修饰影响RNA的稳定性、剪接、翻译和相互作用,从而调控胚胎发育、免疫反应和细胞稳态等关键生物学过程。RNA修饰失调与多种病理状态密切相关。本综述系统地总结了在理解动态RNA修饰如何调控健康与疾病方面的最新进展。我们批判性地回顾了m6A修饰,这是最丰富的RNA甲基化修饰,及其与疾病的关联以及翻译后调控。我们评估了三个相互关联的主题:疾病机制,其中失调的m6A驱动肿瘤发生(例如,METTL3介导的乳腺癌高甲基化)并导致神经精神/心血管疾病;稳态功能,涵盖胚胎发生(母源-合子转变)、组织再生(肌肉中的YTHDF1)和免疫调节;治疗前沿,包括酶靶向策略(FTO抑制剂、METTL3稳定剂)和诊断方法。我们的分析表明,依赖于上下文的RNA修饰网络作为生物学“开关”发挥作用,其失调会引发致病级联反应。我们进一步提出了一个使用多组学整合来靶向这些网络的新框架。本综述将RNA修饰确立为精准医学的核心靶点,同时强调了临床转化中需要跨学科合作的关键挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5503/12409077/d466f912e1eb/MCO2-6-e70341-g006.jpg

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