A critical role of N⁴-acetylation of cytidine in mRNA by NAT10 in T cell expansion and antiviral immunity.

ABSTRACT: Following activation, naive T cells exit quiescence and require global translation for rapid expansion, yet the underlying mechanisms remain unclear. Here, we show that during T cell activation, cells upregulate the expression of N-acetyltransferase 10 (NAT10), an enzyme responsible for N⁴-acetylcytidine (ac⁴C) modification of mRNAs. ac⁴C-modified Myc mRNAs show higher translation efficiency, enabling rapid synthesis of MYC protein and supporting robust T cell expansion. Conditional deletion of Nat10 in mouse T cells causes severe cell cycle arrest and limitation of cell expansion due to MYC deficiency, ultimately exacerbating infection in an acute lymphocytic choriomeningitis virus model. Additionally, T cells from older individuals with lower NAT10 levels

SUBMITTER: Sun L 

PROVIDER: S-EPMC11957992 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature