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Review
. 2025 Aug 13:13:1623276.
doi: 10.3389/fcell.2025.1623276. eCollection 2025.

Research progress on NAT10-mediated acetylation in normal development and disease

Da Qin  1 , Qing Liu  1 , Xiaochao Ma  1 , Rui Wang  1 , Tianyu Lu  1 , Yue Yang  1 , Ze Tang  1 , Yanbo Zhu  2
Affiliations
Review

Research progress on NAT10-mediated acetylation in normal development and disease

Da Qin et al. Front Cell Dev Biol. .

Abstract

N4-acetylcytidine (ac4C) is an evolutionarily conserved RNA modification catalyzed by the acetyltransferase NAT10. It regulates RNA stability, translation, and post-transcriptional processes. Meanwhile, NAT10 functions as a dual-function enzyme exhibiting both protein acetyltransferase and RNA acetylase activities. This review summarizes the structural and functional roles of NAT10-mediated acetylation in physiological contexts, including cell division, differentiation, inflammation, aging, and viral infection, as well as its emerging roles in cancer. In malignancies, NAT10-mediated acetylation drives tumor progression by enhancing mRNA stability, regulating cell cycle, promoting metastasis, suppressing ferroptosis, modulating metabolism, influencing p53 activity, mediating immune escape and fostering drug resistance. Interactions between NAT10 and non-coding RNAs further amplify its oncogenic effects. Unresolved questions, such as microbiota-mediated ac4C regulation and NAT10's impact on the tumor immune microenvironment, highlight future research directions. Targeting NAT10 and ac4C modification presents promising therapeutic opportunities, with advanced technologies like single-cell sequencing poised to refine epitranscriptome-based interventions.

Keywords: AC4C; NAT10; RNA modification; cancer; epitranscriptomics; therapeutic target.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
NAT10: Structural characteristics and molecular roles. (A) Linear representation of the NAT10 protein. (B) Three-dimensional structure of NAT10 obtained from AlphaFold (ID: AF-Q9H0A0-F1), with protein domains visually distinguished using PyMOL. (C) Functional overview of NAT10 in tRNA, rRNA, and mRNA.
FIGURE 2
FIGURE 2
Summary of the roles of NAT10-mediated RNA and protein acetylation in normal cells.
FIGURE 3
FIGURE 3
NAT10 and ac4C mechanisms in multiple tumors. Mechanisms of NAT10 and ac4C modification in colon, breast, gastric, liver, cervical, bladder, and pancreatic cancers.
FIGURE 4
FIGURE 4
Mechanisms of NAT10 and ac4C in enhancing mRNA stability in cancer.
FIGURE 5
FIGURE 5
Summary of NAT10 and ac4C in modulating ferroptosis and metabolic mechanisms.
FIGURE 6
FIGURE 6
NAT10-mediated acetylation: regulatory mechanisms in cancer.
See this image and copyright information in PMC

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