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A previous report shows that Staufen1, a cellular double-stranded (ds) RNA-binding protein (RBP), binds to the 5\u2019untranslated region (5\u2032UTR) 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.<\/jats:p>","DOI":"10.1093\/nar\/gkab1188","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T20:12:48Z","timestamp":1637093568000},"page":"411-429","source":"Crossref","is-referenced-by-count":23,"title":["The double-stranded RNA-binding protein, Staufen1, is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation"],"prefix":"10.1093","volume":"50","author":[{"given":"Hade","family":"Ramos","sequence":"first","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Instituto Milenio de Inmunolog\u00eda e Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunolog\u00eda Pedi\u00e1trica, Escuela de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Marcoleta 391, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Monette","sequence":"additional","affiliation":[{"name":"HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montr\u00e9al, Qu\u00e9bec H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijuan","family":"Niu","sequence":"additional","affiliation":[{"name":"HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montr\u00e9al, Qu\u00e9bec H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Barrera","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Instituto Milenio de Inmunolog\u00eda e Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunolog\u00eda Pedi\u00e1trica, Escuela de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Marcoleta 391, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"L\u00f3pez-Ulloa","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Instituto Milenio de Inmunolog\u00eda e Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunolog\u00eda Pedi\u00e1trica, Escuela de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Marcoleta 391, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazm\u00edn","family":"Fuentes","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Instituto Milenio de Inmunolog\u00eda e Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunolog\u00eda Pedi\u00e1trica, Escuela de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Marcoleta 391, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Guizar","sequence":"additional","affiliation":[{"name":"HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montr\u00e9al, Qu\u00e9bec H3T 1E2, Canada"},{"name":"Department of Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec\u00a0H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Pino","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Instituto Milenio de Inmunolog\u00eda e Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunolog\u00eda Pedi\u00e1trica, Escuela de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Marcoleta 391, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1511-8998","authenticated-orcid":false,"given":"Luc","family":"DesGroseillers","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Medicine, University of Montreal, P.O. Box 6128, Station Centre Ville, Montreal, Qu\u00e9bec H3C 3J7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1828-0296","authenticated-orcid":false,"given":"Andrew\u00a0J","family":"Mouland","sequence":"additional","affiliation":[{"name":"HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital, Montr\u00e9al, Qu\u00e9bec H3T 1E2, Canada"},{"name":"Department of Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec\u00a0H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7936-8478","authenticated-orcid":false,"given":"Marcelo","family":"L\u00f3pez-Lastra","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Instituto Milenio de Inmunolog\u00eda e Inmunoterapia, Departamento de Enfermedades Infecciosas e Inmunolog\u00eda Pedi\u00e1trica, Escuela de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Marcoleta 391, Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"key":"2022011223472928300_B1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nrm2838","article-title":"The mechanism of eukaryotic translation initiation and principles of its regulation","volume":"11","author":"Jackson","year":"2010","journal-title":"Nat. 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