Structure of the NAT10 acetyltransferase and mechanism of tRNA acetylation (opens in new tab)

NAT10 is the sole eukaryotic acetyltransferase that catalyzes N4-acetylcytidine (ac4C) modification of RNA. While dysregulation of NAT10 is associated with cancer and premature aging syndromes, the requirement for its acetyltransferase activity and how NAT10 coordinates catalysis and RNA binding remain poorly understood. Here, we report single particle cryo-electron microscopy structures of eukaryotic (Chaetomium thermophilum) NAT10 in complex with a designer cytidine-CoA cofactor-based ligan...