Human NAT10 Is an ATP-dependent RNA Acetyltransferase Responsible for N4-Acetylcytidine Formation in 18 S Ribosomal RNA (rRNA)

Human N -acetyltransferase 10 (NAT10) is known to be a lysine acetyltransferase that targets microtubules and histones and plays an important role in cell division. NAT10 is highly expressed in malignant tumors, and is also a promising target for therapies against laminopathies and premature aging. Here we report that NAT10 is an ATP-dependent RNA acetyltransferase responsible for formation of N 4 -acetylcytidine (ac 4 C) at position 1842 in the terminal helix of mammalian 18 S rRNA. RNAi-mediated knockdown of NAT10 resulted in growth retardation of human cells, and this was accompanied by high-level accumulation of the 30 S precursor of 18 S rRNA, suggesting that ac 4 C1842 formation catalyzed by NAT10 is involved in rRNA processing and ribosome biogenesis.Post-transcriptional modifications of rRNAs play important roles in biogenesis and function of ribosome. Results NAT10 is an ATP-dependent RNA acetyltransferase responsible for N 4 -acetylcytidine formation of 18 S rRNA. Conclusion NAT10 and ac 4 C1842 are required for pre-18 S rRNA processing. Significance 40 S subunit formation is regulated by a single acetylation of 18 S rRNA, implying a regulatory mechanism for ribosome biogenesis by sensing the cellular energy budget.