Institute of Biomedical Research, Department of Infectious Diseases, Regulatory Mechanism and Targeted Therapy for Liver Cancer Shiyan Key Laboratory, Hubei rovincial Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, China; Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, China.
Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China.
Pharmacol Ther. 2024 Jan;253:108576. doi: 10.1016/j.pharmthera.2023.108576. Epub 2023 Dec 7.
RNA ac4C modification is a novel and rare chemical modification observed in mRNA. Traditional biochemical studies had primarily associated ac4C modification with tRNA and rRNA until in 2018, Arango D et al. first reported the presence of ac4C modification on mRNA and demonstrated its critical role in mRNA stability and translation regulation. Furthermore, they established that the ac4C modification on mRNA is mediated by the classical N-acetyltransferase NAT10. Subsequent studies have underscored the essential implications of NAT10 and mRNA ac4C modification across both physiological and pathological regulatory processes. In this review, we aimed to explore the discovery history of RNA ac4C modification, its detection methods, and its regulatory mechanisms in disease and physiological development. We offer a forward-looking examination and discourse concerning the employment of RNA ac4C modification as a prospective therapeutic strategy across diverse diseases. Furthermore, we comprehensively summarize the functions and mechanisms of NAT10 in gene expression regulation and pathogenesis independent of RNA ac4C modification.
RNA ac4C 修饰是一种在 mRNA 中观察到的新型稀有化学修饰。传统的生化研究主要将 ac4C 修饰与 tRNA 和 rRNA 相关联，直到 2018 年，Arango D 等人首次报道了 mRNA 上存在 ac4C 修饰，并证明了它在 mRNA 稳定性和翻译调控中的关键作用。此外，他们还证实，mRNA 上的 ac4C 修饰是由经典的 N-乙酰转移酶 NAT10 介导的。随后的研究强调了 NAT10 和 mRNA ac4C 修饰在生理和病理调节过程中的重要意义。在这篇综述中，我们旨在探讨 RNA ac4C 修饰的发现历史、检测方法以及其在疾病和生理发育中的调控机制。我们对 RNA ac4C 修饰作为一种有前途的治疗策略在多种疾病中的应用进行了前瞻性的考察和讨论。此外，我们还全面总结了 NAT10 在基因表达调控和发病机制中的功能和机制，而不依赖于 RNA ac4C 修饰。
