The double-stranded RNA-binding protein, Staufen1 is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation

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dc.contributor.authorRamos, Hade
dc.contributor.authorMonette, Anne
dc.contributor.authorNiu, Meijuan
dc.contributor.authorBarrera, Aldo
dc.contributor.authorLopez-Ulloa, Brenda
dc.contributor.authorFuentes, Yazmin
dc.contributor.authorGuizar, Paola
dc.contributor.authorPino, Karla
dc.contributor.authorDesGroseillers, Luc
dc.contributor.authorMouland, Andrew J.
dc.contributor.authorLopez-Lastra, Marcelo
dc.date.accessioned2025-01-20T22:00:30Z
dc.date.available2025-01-20T22:00:30Z
dc.date.issued2022
dc.description.abstractTranslation 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 Staufenl-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.
dc.fuente.origenWOS
dc.identifier.doi10.1093/nar/gkab1188
dc.identifier.eissn1362-4962
dc.identifier.issn0305-1048
dc.identifier.urihttps://doi.org/10.1093/nar/gkab1188
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/93729
dc.identifier.wosidWOS:000749588900033
dc.issue.numero1
dc.language.isoen
dc.pagina.final429
dc.pagina.inicio411
dc.revistaNucleic acids research
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe double-stranded RNA-binding protein, Staufen1 is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation
dc.typeartículo
dc.volumen50
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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