Lactylation of NAT10 promotes N 4 -acetylcytidine modification on tRNA Ser-CGA-1-1 to boost oncogenic DNA virus KSHV reactivation.

Autor: Yan Q; Department of Microbiology, Nanjing Medical University, Nanjing, 211166, PR China. yanqin@njmu.edu.cn.; Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, 211166, PR China. yanqin@njmu.edu.cn.; Changzhou Medical Center, Nanjing Medical University, Nanjing, 211166, PR China. yanqin@njmu.edu.cn., Zhou J; Department of Microbiology, Nanjing Medical University, Nanjing, 211166, PR China.; Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, 211166, PR China., Gu Y; Department of Microbiology, Nanjing Medical University, Nanjing, 211166, PR China.; Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, 211166, PR China., Huang W; Department of Microbiology, Nanjing Medical University, Nanjing, 211166, PR China.; Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, 211166, PR China., Ruan M; Department of Microbiology, Nanjing Medical University, Nanjing, 211166, PR China.; Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, 211166, PR China., Zhang H; Department of Microbiology, Nanjing Medical University, Nanjing, 211166, PR China.; Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, 211166, PR China., Wang T; Department of Microbiology, Nanjing Medical University, Nanjing, 211166, PR China.; Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, 211166, PR China., Wei P; Department of Microbiology, Nanjing Medical University, Nanjing, 211166, PR China.; Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, 211166, PR China., Chen G; Changzhou Medical Center, Nanjing Medical University, Nanjing, 211166, PR China. guochunchen1503@163.com.; Department of Infectious Diseases, Changzhou Third People's Hospital, Changzhou, 213000, PR China. guochunchen1503@163.com., Li W; Department of Microbiology, Nanjing Medical University, Nanjing, 211166, PR China. wanli@njmu.edu.cn.; Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, 211166, PR China. wanli@njmu.edu.cn.; Changzhou Medical Center, Nanjing Medical University, Nanjing, 211166, PR China. wanli@njmu.edu.cn., Lu C; Department of Microbiology, Nanjing Medical University, Nanjing, 211166, PR China. clu@njmu.edu.cn.; Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, 211166, PR China. clu@njmu.edu.cn.; Changzhou Medical Center, Nanjing Medical University, Nanjing, 211166, PR China. clu@njmu.edu.cn.
Jazyk: angličtina
Zdroj: Cell death and differentiation [Cell Death Differ] 2024 Oct; Vol. 31 (10), pp. 1362-1374. Date of Electronic Publication: 2024 Jun 15.
DOI: 10.1038/s41418-024-01327-0
Abstrakt: N 4 -acetylcytidine (ac 4 C), a conserved but recently rediscovered RNA modification on tRNAs, rRNAs and mRNAs, is catalyzed by N-acetyltransferase 10 (NAT10). Lysine acylation is a ubiquitous protein modification that controls protein functions. Our latest study demonstrates a NAT10-dependent ac 4 C modification, which occurs on the polyadenylated nuclear RNA (PAN) encoded by oncogenic DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV), can induce KSHV reactivation from latency and activate inflammasome. However, it remains unclear whether a novel lysine acylation occurs in NAT10 during KSHV reactivation and how this acylation of NAT10 regulates tRNAs ac 4 C modification. Here, we showed that NAT10 was lactylated by α-tubulin acetyltransferase 1 (ATAT1), as a writer at the critical domain, to exert RNA acetyltransferase function and thus increase the ac 4 C level of tRNA Ser-CGA-1-1 . Mutagenesis at the ac 4 C site in tRNA Ser-CGA-1-1 inhibited its ac 4 C modifications, translation efficiency of viral lytic genes, and virion production. Mechanistically, KSHV PAN orchestrated NAT10 and ATAT1 to enhance NAT10 lactylation, resulting in tRNA Ser-CGA-1-1 ac 4 C modification, eventually boosting KSHV reactivation. Our findings reveal a novel post-translational modification in NAT10, as well as expand the understanding about tRNA-related ac 4 C modification during KSHV replication, which may be exploited to design therapeutic strategies for KSHV-related diseases.
(© 2024. The Author(s).)
Databáze: MEDLINE
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