Epitranscriptomic regulation of HIV-1 full-length RNA packaging.
Nucleic Acids Res
; 50(4): 2302-2318, 2022 02 28.
Article
en En
| MEDLINE
| ID: mdl-35137199
ABSTRACT
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 N6-methyladenosine (m6A) regulates full-length RNA packaging. While m6A 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 m6A 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
VIH-1
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2022
Tipo del documento:
Article
País de afiliación:
Chile