Human lysyl-tRNA synthetase phosphorylation promotes HIV-1 proviral DNA transcription

Yingke Tang; Ryan T Behrens; Corine St Gelais; Siqi Wu; Saravanan Vivekanandan; Ehud Razin; Pengfei Fang; Li Wu; Nathan Sherer; Karin Musier-Forsyth

doi:10.1093/nar/gkad941

Back

Human lysyl-tRNA synthetase phosphorylation promotes HIV-1 proviral DNA transcription

Journal article

Open access

Peer reviewed

Human lysyl-tRNA synthetase phosphorylation promotes HIV-1 proviral DNA transcription

Yingke Tang, Ryan T Behrens, Corine St Gelais, Siqi Wu, Saravanan Vivekanandan, Ehud Razin, Pengfei Fang, Li Wu, Nathan Sherer and Karin Musier-Forsyth

Nucleic acids research, Vol.51(22), pp.12111-12123

12/11/2023

DOI: 10.1093/nar/gkad941

PMCID: PMC10711549

PMID: 37933844

Files and links (1)

url

https://doi.org/10.1093/nar/gkad941View

Published (Version of record) Open Access

Abstract

Abstract Human lysyl-tRNA synthetase (LysRS) was previously shown to be re-localized from its normal cytoplasmic location in a multi-aminoacyl-tRNA synthetase complex (MSC) to the nucleus of HIV-1 infected cells. Nuclear localization depends on S207 phosphorylation but the nuclear function of pS207-LysRS in the HIV-1 lifecycle is unknown. Here, we show that HIV-1 replication was severely reduced in a S207A-LysRS knock-in cell line generated by CRISPR/Cas9; this effect was rescued by S207D-LysRS. LysRS phosphorylation up-regulated HIV-1 transcription, as did direct transfection of Ap4A, an upstream transcription factor 2 (USF2) activator that is synthesized by pS207-LysRS. Overexpressing an MSC-derived peptide known to stabilize LysRS MSC binding inhibited HIV-1 replication. Transcription of HIV-1 proviral DNA and other USF2 target genes was reduced in peptide-expressing cells. We propose that nuclear pS207-LysRS generates Ap4A, leading to activation of HIV-1 transcription. Our results suggest a new role for nuclear LysRS in facilitating HIV-1 replication and new avenues for antiviral therapy.

Details

Title: Subtitle: Human lysyl-tRNA synthetase phosphorylation promotes HIV-1 proviral DNA transcription
Creators: Yingke Tang
Ryan T Behrens - University of Wisconsin Carbone Cancer Center
Corine St Gelais
Siqi Wu - Shanghai Institute of Organic Chemistry
Saravanan Vivekanandan - National University of Singapore
Ehud Razin - Hebrew University of Jerusalem
Pengfei Fang - Shanghai Institute of Organic Chemistry
Li Wu - University of Iowa
Nathan Sherer - University of Wisconsin Carbone Cancer Center
Karin Musier-Forsyth
Resource Type: Journal article
Publication Details: Nucleic acids research, Vol.51(22), pp.12111-12123
DOI: 10.1093/nar/gkad941
PMID: 37933844
PMCID: PMC10711549
NLM abbreviation: Nucleic Acids Res
ISSN: 0305-1048
eISSN: 1362-4962
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 AI150493, R61 AI169659, R21 AI170070, R01AI110221; DOI: 10.13039/501100003977, name: Israel Science Foundation, award: 331/20; DOI: 10.13039/501100001809, name: National Natural Science Foundation of China, award: 21977107
Language: English
Electronic publication date: 11/02/2023
Date published: 12/11/2023
Academic Unit: Microbiology and Immunology
Record Identifier: 9984507026702771

Metrics

8 Record Views

3 Times Cited - Web of Science