RNA Modifications: Current Understandings and Future Perspectives

RNA modification has been established as a pivotal field in epitranscriptomics, representing an emerging, dynamic, and precise regulatory layer in gene expression control. N6-methyladenosine (m⁶A), the most prevalent internal RNA modification, is critical for post-transcriptional regulation of RNA stability, translation, and degradation. In addition to m⁶A, RNA contains a number of other modifications that play important regulatory roles in RNA metabolism, transport, translation, and stability. Our review uses N4-acetylcytidine (ac4C) modification as a research paradigm to conduct a systematic review of the RNA modification research framework. This article begins with RNA modifications, then discusses several RNA modification-related regulatory enzymes before using ac4C as a detailed research example. Starting with the fundamental functions of ac4C in RNA modifications, it discusses its discovery history, the specific mechanisms of the key acetyltransferase N-acetyltransferase 10 (NAT10) in various RNA modifications, existing detection technologies, and the functional significance of ac4C modification under physiological and pathological conditions. This review systematically explains the multidimensional roles of RNA modifications, represented by ac4C, in health and disease. We point out that RNA modification-related regulatory enzymes, such as NAT10, can serve as prognostic biomarkers and therapeutic targets, thereby advancing disease mechanism research and improving clinical diagnosis and treatment.