The molecular mechanisms underlying NAT10-mediated RNA ac4C modification and protein acetylation, as well as their biological functions across physiological and pathological contexts, are systematically summarized, with the aim of facilitating its clinical translation.
Abstract
The rapid advances in epigenetic and epitranscriptomic regulatory mechanisms have opened new prospects for precision therapies in various diseases. N-acetyltransferase 10 (NAT10) is currently the only known eukaryotic RNA ac4C acetyltransferase and has also been reported to acetylate multiple protein substrates, regulating diverse physiological processes. In this review, we comprehensively describe the domain organization, structural features and subcellular localization of NAT10. The molecular mechanisms underlying NAT10-mediated RNA ac4C modification and protein acetylation, as well as their biological functions across physiological and pathological contexts, are systematically summarized, with the aim of facilitating its clinical translation. Furthermore, we review the recent advances in NAT10-targeted therapeutic strategies, discuss the potential for combining NAT10-targeted strategies with existing treatment modalities, and propose possible approaches for optimization. By integrating current evidence, this review provides insights into the functions of NAT10 and highlights future research directions for its validation and translational development as a clinical therapeutic target in various diseases.
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