Emerging roles of RNA ac4C modification and NAT10 in mammalian development and human diseases

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.