The Processing, Gene Regulation, Biological Functions, and Clinical Relevance of N4-Acetylcytidine on RNA: A Systematic Review

N4-acetylcytidine (ac4C) is often considered to be a conservative, chemically modified nucleoside present on tRNA and rRNA. Recent studies have shown extensive ac4C modifications in human and yeast mRNAs. ac4C helps to correctly read codons during translation and improves translation efficiency and the stability of mRNA. At present, the research of ac4C involves a variety of detection methods. The formation of ac4C is closely related to N-acetyltransferase 10 (NAT10) and its helpers, such as putative tRNA acetyltransferase (TAN1) for tRNA ac4C and small nucleolar RNA (snoRNA) for rRNA ac4C. Also, ac4C is associated with the development, progression, and prognosis of a variety of human diseases. Here, we summarize the history of ac4C research and the detection technologies of ac4C. We then summarized the role and mechanism of ac4C in gene-expression regulation and demonstrated the relevance of ac4C to a variety of human diseases, especially cancer. Finally, we list the future challenges of the ac4C research and demonstrate a research strategy for the interactions among several abundant modified nucleosides on mRNA.