PXD049447

PXD049447 is an original dataset announced via ProteomeXchange.

Title	Lactylation of NAT10 promotes N4‐acetylcytidine modification on tRNASer-CGA-1-1 to boost oncogenic DNA virus KSHV reactivation
Description	N4-acetylcytidine (ac4C), 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 ac4C 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 ac4C 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 ac4C level of tRNASer-CGA-1-1. Mutagenesis at the ac4C site in tRNASer-CGA-1-1 inhibited its ac4C modifications, translation efficiency of viral lytic genes, and virion production. Mechanistically, KSHV PAN orchestrated NAT10 and ATAT1 to enhance NAT10 lactylation, resulting in tRNASer-CGA-1-1 ac4C modification, eventually boosting KSHV reactivation. Our findings reveal a novel post-translational modification in NAT10, as well as expand the understanding about tRNA-related ac4C modification during KSHV replication, which may be exploited to design therapeutic strategies for KSHV-related diseases.
HostingRepository	iProX
AnnounceDate	2024-04-26
AnnouncementXML	Submission_2024-06-17_00:46:13.059.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jing Zhou
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-17 18:43:19	ID requested
1	2024-02-17 18:43:54	announced
⏵ 2	2024-06-17 00:46:14	announced	2024-06-17: Update information.

Yan Q, Zhou J, Gu Y, Huang W, Ruan M, Zhang H, Wang T, Wei P, Chen G, Li W, Lu C, to boost oncogenic DNA virus KSHV reactivation. Cell Death Differ, 31(10):1362-1374(2024) [pubmed]

submitter keyword: KSHV, NAT10, lactylation, N4‐acetylcytidine, lytic reactivation

Chun Lu
contact affiliation	Nanjing Medical University
contact email	clu@njmu.edu.cn
lab head
Jing Zhou
contact affiliation	Nanjing Medical University
contact email	jsbyzhoujing@163.com
dataset submitter

iProX dataset URI