PXD049447-1

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	2024-02-18
AnnouncementXML	Submission_2024-02-17_18:43:53.814.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	4800 Plus MALDI TOF/TOF; 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.

Dataset with its publication pending

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