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 修饰是在 mRNA 中观察到的一种新颖且罕见的化学修饰。 Arango D 等人在 2018 年之前一直将 ac4C 修饰与 tRNA 和 rRNA 联系起来。首次报道了 mRNA 上 ac4C 修饰的存在，并证明了其在 mRNA 稳定性和翻译调控中的关键作用。此外，他们还确定 mRNA 上的 ac4C 修饰是由经典 N-乙酰转移酶 NAT10 介导的。随后的研究强调了 NAT10 和 mRNA ac4C 修饰对生理和病理调节过程的重要影响。在这篇综述中，我们旨在探讨RNA ac4C修饰的发现历史、其检测方法及其在疾病和生理发展中的调控机制。我们提供关于 RNA ac4C 修饰作为多种疾病的前瞻性治疗策略的前瞻性研究和讨论。此外，我们全面总结了NAT10在不依赖RNA ac4C修饰的基因表达调控和发病机制中的功能和机制。