{"doi":"10.1093/nar/gkab1188","title":"The double-stranded RNA-binding protein, Staufen1, is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation","abstract":"Translation initiation of the viral genomic mRNA (vRNA) of human immunodeficiency virus-type 1 (HIV-1) can be mediated by a cap- or an internal ribosome entry site (IRES)-dependent mechanism. A previous report shows that Staufen1, a cellular double-stranded (ds) RNA-binding protein (RBP), binds to the 5'untranslated region (5'UTR) of the HIV-1 vRNA and promotes its cap-dependent translation. In this study, we now evaluate the role of Staufen1 as an HIV-1 IRES-transacting factor (ITAF). We first confirm that Staufen1 associates with both the HIV-1 vRNA and the Gag protein during HIV-1 replication. We found that in HIV-1-expressing cells, siRNA-mediated depletion of Staufen1 reduces HIV-1 vRNA translation. Using dual-luciferase bicistronic mRNAs, we show that the siRNA-mediated depletion and cDNA-mediated overexpression of Staufen1 acutely regulates HIV-1 IRES activity. Furthermore, we show that Staufen1-vRNA interaction is required for the enhancement of HIV-1 IRES activity. Interestingly, we find that only Staufen1 harboring an intact dsRNA-binding domain 3 (dsRBD3) rescues HIV-1 IRES activity in Staufen1 CRISPR-Cas9 gene edited cells. Finally, we show that the expression of Staufen1-dsRBD3 alone enhances HIV-1 IRES activity. This study provides evidence of a novel role for Staufen1 as an ITAF promoting HIV-1 vRNA IRES activity.","journal":"Nucleic Acids Research","year":2021,"id":176930,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":271419,"name":"Anne Monette","orcid":"0000-0002-1940-5046","position":1,"is_corresponding":false},{"id":272967,"name":"Meijuan Niu","orcid":null,"position":2,"is_corresponding":false},{"id":270035,"name":"Aldo Barrera","orcid":"0000-0002-3748-2387","position":3,"is_corresponding":false},{"id":720371,"name":"Brenda López‐Ulloa","orcid":"0000-0002-3023-3038","position":4,"is_corresponding":false},{"id":721192,"name":"Yazmín Fuentes","orcid":null,"position":5,"is_corresponding":false},{"id":721193,"name":"Paola Guizar","orcid":null,"position":6,"is_corresponding":false},{"id":721194,"name":"Karla Pino","orcid":null,"position":7,"is_corresponding":false},{"id":720372,"name":"Luc DesGroseillers","orcid":"0000-0002-1511-8998","position":8,"is_corresponding":false},{"id":271422,"name":"Andrew J. Mouland","orcid":"0000-0002-1828-0296","position":9,"is_corresponding":false},{"id":720373,"name":"Marcelo López‐Lastra","orcid":"0000-0002-7936-8478","position":10,"is_corresponding":false},{"id":721191,"name":"Hade Ramos","orcid":null,"position":0,"is_corresponding":true}],"reference_count":95,"raw_metadata":null,"created_at":"2026-07-18T23:47:28.018172Z","pmid":"34893869","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":[]}