RT info:eu-repo/semantics/article T1 A conserved uORF regulates APOBEC3G translation and is targeted by HIV-1 Vif protein to repress the antiviral factor A1 Valenzuela Fernández, Agustín A1 Libre, Camille A1 Seissler, Tanja A1 Guerrero, Santiago A1 Batisse, Julien A1 Verriez, Cédric A1 Stupfler, Benjamin A1 Gilmer, Orian A1 Cabrera Rodriguez, Romina A1 Weber, Melanie M. A1 Cimarelli, Andrea A1 Etienne, Lucie A1 Marquet, Roland A1 Paillart, Jean-Christophe A2 Medicina Física y Farmacología A2 Grupo "Inmunología Celular y Viral". AB The HIV-1 Vif protein is essential for viral fitness and pathogenicity. Vif decreases expression ofcellular restriction factors APOBEC3G (A3G), A3F, A3D and A3H, which inhibit HIV-1 replication byinducing hypermutation during reverse transcription. Vif counteracts A3G at several levels(transcription, translation and protein degradation) that together reduce the levels of A3G in cells andprevent its incorporation into viral particles. How Vif affects A3G translation remains unclear. Here, weuncovered the importance of a short conserved uORF (upstream ORF) located within two criticalstem-loop structures of the 5’ untranslated region (5’UTR) of A3G mRNA for this process. A3Gtranslation occurs through a combination of leaky-scanning and translation re-initiation and thepresence of an intact uORF decreases the extent of global A3G translation under normal conditions.Interestingly, the uORF is also absolutely required for Vif-mediated translation inhibition andredirection of A3G mRNA into stress granules. Overall, we discovered that A3G translation isregulated by a small uORF conserved in the human population and that Vif uses this specific featureto repress its translation YR 2021 FD 2021 LK http://riull.ull.es/xmlui/handle/915/35350 UL http://riull.ull.es/xmlui/handle/915/35350 LA en NO bioRxiv preprint doi: https://doi.org/10.1101/2021.01.13.426487; this version posted October 8, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. DS Repositorio institucional de la Universidad de La Laguna RD 23-may-2024