{"doi":"10.1093/nar/gkad941","title":"Human lysyl-tRNA synthetase phosphorylation promotes HIV-1 proviral DNA transcription","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.","journal":"Nucleic Acids Research","year":2023,"id":364811,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":786859,"name":"Ryan T. Behrens","orcid":"0000-0001-5761-9056","position":1,"is_corresponding":false},{"id":577884,"name":"Corine St. Gelais","orcid":null,"position":2,"is_corresponding":false},{"id":1119905,"name":"Siqi Wu","orcid":"0000-0002-2442-5041","position":3,"is_corresponding":false},{"id":1120369,"name":"Saravanan Vivekanandan","orcid":null,"position":4,"is_corresponding":false},{"id":1119906,"name":"Ehud Razin","orcid":"0000-0001-8041-3718","position":5,"is_corresponding":false},{"id":1062598,"name":"Pengfei Fang","orcid":"0000-0002-3448-5494","position":6,"is_corresponding":false},{"id":576943,"name":"Li Wu","orcid":"0000-0002-5468-2487","position":7,"is_corresponding":false},{"id":461939,"name":"Nathan M. Sherer","orcid":"0000-0001-9974-236X","position":8,"is_corresponding":false},{"id":377519,"name":"Karin Musier‐Forsyth","orcid":null,"position":9,"is_corresponding":false},{"id":1120368,"name":"Yingke Tang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T01:14:41.218128Z","pmid":"37933844","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}