Epitranscriptomic regulation of HIV-1 full-length RNA packaging

Pereira-Montecinos, Camila; Toro-Ascuy, Daniela; Ananias-Saez, Catarina; Gaete-Argel, Aracelly; Rojas-Fuentes, Cecilia; Riquelme-Barrios, Sebastian; Rojas-Araya, Barbara; Garcia-de-Gracia, Francisco; Aguilera-Cortes, Paulina; Chnaiderman, Jonas; Acevedo, Monica L.; Valiente-Echeverria, Fernando; Soto-Rifo, Ricardo


During retroviral replication, the full-length RNA serves both as mRNA and genomic RNA. However, the mechanisms by which the HIV-1 Gag protein selects the two RNA molecules that will be packaged into nascent virions remain poorly understood. Here, we demonstrate that deposition of N-6-methyladenosine (m(6)A) regulates full-length RNA packaging. While m(6)A deposition by METTL3/METTL14 onto the full-length RNA was associated with increased Gag synthesis and reduced packaging, FTO-mediated demethylation promoted the incorporation of the full-length RNA into viral particles. Interestingly, HIV-1 Gag associates with the RNA demethylase FTO in the nucleus and contributes to full-length RNA demethylation. We further identified two highly conserved adenosines within the 5 '-UTR that have a crucial functional role in m(6)A methylation and packaging of the full-length RNA. Together, our data propose a novel epitranscriptomic mechanism allowing the selection of the HIV-1 full-length RNA molecules that will be used as viral genomes.

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Título según WOS: Epitranscriptomic regulation of HIV-1 full-length RNA packaging
Título de la Revista: NUCLEIC ACIDS RESEARCH
Volumen: 50
Número: 4
Fecha de publicación: 2022
Página de inicio: 2302
Página final: 2318


Notas: ISI