RNA Cytidine Acetyltransferase NAT10 Maintains T Cell Pathogenicity in Inflammatory Bowel Disease

The enzyme N-acetyltransferase 10 (NAT10), known as the exclusive catalyst for N4-acetylcytidine (ac4C) modification, has been associated with various cellular processes, including tRNA acetylation, 18S rRNA biogenesis, mRNA stability, and translational efficiency. Despite extensive investigation into its molecular mechanisms in vitro, the physiological function of NAT10 under normal conditions has remained largely undefined. In this study, we found that the deficiency of NAT10 led to a disruption of T cell development at steady state, and identified a pivotal role for NAT10 in preserving the pathogenicity of naïve CD4+ T cells to induce adoptive transfer colitis. Mechanistically, the lack of NAT10 triggers the diminished stability of the anti-apoptotic gene Bag3, initiating a cascade of events that includes the upregulation of apoptosis-related genes and an accelerated rate of apoptosis in T cells. Our findings reveal a previously unrecognized role of the NAT10-ac4C-Bag3 axis in maintaining T cell homeostasis in vivo. Overall design: We isolated naïve CD4+ T cells from 3 WT and 3 Nat10 cKO mice for RNA-sequencing.