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细胞代谢中的 RNA 修饰:对代谢靶向治疗和免疫治疗的影响。

RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy.

机构信息

Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

School of Clinical Medicine, Shandong University, Jinan, China.

出版信息

Signal Transduct Target Ther. 2024 Mar 27;9(1):70. doi: 10.1038/s41392-024-01777-5.

Abstract

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding of pathophysiology, and inspiring development of therapeutics. As a crucial component of epigenetics at post-transcription level, RNA modification significantly determines RNA fates, further affecting various biological processes and cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts. In this review, we characterize the distribution features, modifying mechanisms and biological functions of 8 RNA modifications, including N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively the most studied types. Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described, categorized as glucose, lipid, amino acid, and mitochondrial metabolism. And we highlight the regulation of RNA modifications on immunometabolism, further influencing immune responses. Above all, we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy, progression of RNA modification-targeted agents, and its potential in RNA-targeted therapeutics. Eventually, we give legitimate perspectives for future researches in this field from methodological requirements, mechanistic insights, to therapeutic applications.

摘要

细胞代谢是一个复杂的网络,满足细胞的生物能量学和生物合成需求。相关研究不断深入我们对病理生理学的理解,并为治疗方法的发展提供了灵感。作为转录后水平表观遗传学的重要组成部分,RNA 修饰显著决定了 RNA 的命运,进一步影响各种生物过程和细胞表型。值得注意的是,免疫代谢定义了不同阶段和免疫学背景下免疫细胞发生的代谢改变。在这篇综述中,我们描述了 8 种 RNA 修饰(包括 N6-甲基腺苷(m6A)、N6,2'-O-二甲基腺苷(m6Am)、N1-甲基腺苷(m1A)、5-甲基胞嘧啶(m5C)、N4-乙酰胞嘧啶(ac4C)、N7-甲基鸟苷(m7G)、假尿嘧啶(Ψ)、腺苷到肌苷(A-to-I)编辑)的分布特征、修饰机制和生物学功能,这些修饰是目前研究最多的类型。然后,我们全面描述了这些 RNA 修饰在不同健康和疾病背景下代谢中的调节作用,分为葡萄糖、脂质、氨基酸和线粒体代谢。我们强调了 RNA 修饰对免疫代谢的调节作用,进一步影响免疫反应。总之,我们深入讨论了 RNA 修饰在代谢靶向治疗和免疫治疗中的临床意义、RNA 修饰靶向药物的进展及其在 RNA 靶向治疗中的潜在应用。最后,我们从方法学要求、机制见解到治疗应用等方面,为该领域的未来研究提供了合理的展望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba7f/10966055/119389427ad6/41392_2024_1777_Fig1_HTML.jpg

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