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The double-stranded RNA-binding protein, Staufen1, is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation
| Content Provider | Oxford Academic |
|---|---|
| Author | Ramos, Hade Monette, Anne Niu, Meijuan Barrera, Aldo López-Ulloa, Brenda Fuentes, Yazmín Guizar, Paola Pino, Karla DesGroseillers, Luc Mouland, Andrew J López-Lastra, Marcelo |
| Copyright Year | 2022 |
| 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. |
| Related Links | https://academic.oup.com/nar/article-pdf/50/1/411/42148905/gkab1188.pdf |
| Ending Page | 429 |
| Starting Page | 411 |
| File Format | |
| ISSN | 03051048 |
| e-ISSN | 13624962 |
| DOI | 10.1093/nar/gkab1188 |
| Journal | Nucleic Acids Research |
| Issue Number | 1 |
| Volume Number | 50 |
| Language | English |
| Publisher | Oxford Academic |
| Publisher Date | 2022-01-11 |
| Access Restriction | Open |
| Subject Keyword | Science and Mathematics Hiv-1 Internal Ribosome Entry Sites Rna-binding Proteins Protein Overexpression Luciferases |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics |
