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.
A2 Medicina Física y Farmacología
A2 Grup'o "Inmunología Celular y Viral".
K1 HIV-1
K1 APOBEC3G
K1 Vif
K1 mRNA
K1 translation
K1 uORF
AB The HIV-1 Vif protein is essential for viral fitness and pathogenicity. Vif decreases expressionof cellular restriction factors APOBEC3G (A3G), A3F, A3D and A3H, which inhibit HIV-1 replicationby inducing hypermutation during reverse transcription. Vif counteracts A3G at several levels(transcription, translation, and protein degradation) that altogether reduce the levels of A3G incells and prevent its incorporation into viral particles. How Vif affects A3G translation remainsunclear. Here, we uncovered the importance of a short conserved uORF (upstream ORF) locatedwithin two critical stem-loop structures of the 5′ untranslated region (5′-UTR) of A3G mRNA for thisprocess. A3G translation occurs through a combination of leaky scanning and translation re-initiationand the presence of an intact uORF decreases the extent of global A3G translation under normalconditions. Interestingly, the uORF is also absolutely required for Vif-mediated translation inhibitionand redirection 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/915/35376
UL http://riull.ull.es/xmlui/handle/915/35376
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 26-dic-2024