NAT10 and <i>N</i>⁴-acetylcytidine restrain R-loop levels and related inflammatory responses.

ABSTRACT: N⁴-acetylcytidine (ac⁴C) is deposited on diverse RNAs by N-acetyltransferase 10 (NAT10), a protein with high biological relevance for aging and cancer. We performed a comprehensive survey of ac⁴C using metabolic labeling, sodium cyanoborohydride chemical treatment coupled to next-generation sequencing (NGS), and ac⁴C antibody-based cell and molecular biology techniques. Our analysis shows that NAT10-dependent ac⁴C-acetylation is robust in rRNA and specific tRNAs but low/spurious in mRNA. It also revealed an inflammatory signature and mutagenesis at transcriptionally active sites in NAT10-KO cells. This finding led us to explore the role of NAT10 in R-loops, which were recently linked to APOBEC3B-mediated mutagenesis. Our

SUBMITTER: Debnath TK 

PROVIDER: S-EPMC11939041 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature