NAT10-mediated N4-acetylcytidine modification drives RNA splicing of PML to alleviate adipose-derived stem cell senescence and promote diabetic wound healing.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Cellular senescence of adipose-derived stem cells (ADSCs) compromises their therapeutic potential in diabetic wound healing. Alternative splicing produces functionally different variants and serves as a critical regulator of senescence. N-acetyltransferase 10 (NAT10) is known to catalyse N4-acetylcytidine (ac4C) RNA modification, and ac4C modification has been involved in RNA splicing. Nevertheless, how NAT10 functions in ADSCs remain unexplored. The aim of this study was to investigate the involvement of NAT10 in ADSC senescence and its impact on RNA splicing. Methods Senescence was assessed by β-galactosidase staining, western blot analysis of p21 and p16 and qRT-PCR detection of senescence-associated secretory phenotype (SASP) genes. The role of NAT10 in splicing regulation was examined by RT‑PCR. Results NAT10 overexpression mitigated ADSC senescence under high-glucose conditions and augmented the wound repair capability of ADSCs. Mechanistically, NAT10 facilitated ac4C-dependent AS of the PML transcript, driving a switch from the long isoform (PML-FL) to the short isoform (PML-S). PML-FL accelerated cellular senescence, whereas PML-S suppressed it. NAT10 recruited SRSF1 to PML pre-mRNA, leading to ac4C-SRSF1-mediated exon skipping and increased PML-S production. Concurrently, NAT10 reduced the binding of PCBP1 to PML, thereby inhibiting PML-FL generation. Conclu

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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