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Cited by 42RNA modifications and cancerHIV Research and TreatmentRNA regulation and disease

Epitranscriptomic regulation of HIV-1 full-length RNA packaging

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Pereira-Montecinos, Camila, Toro-Ascuy, Daniela, Ananías-Sáez, Catarina, Gaete-Argel, Aracelly, Rojas-Fuentes, Cecilia, Riquelme-Barrios, Sebastián, Rojas-Araya, Bárbara, García-de-Gracia, Francisco +5 more·2022·Nucleic Acids Research
DOI 10.1093/nar/gkac062PMC PMC8887480
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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.

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Authors
Pereira-Montecinos, C., Toro-Ascuy, D., Ananías-Sáez, C., Gaete-Argel, A., Rojas-Fuentes, C., Riquelme-Barrios, S., Rojas-Araya, B., García-de-Gracia, F., Aguilera-Cortés, P., Chnaiderman, J., Acevedo, M. L., Valiente-Echeverría, F., & Soto-Rifo, R.
Affiliations
  • University of Chile (CL)
  • Laboratory of Molecular and Cellular Virology, Virology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile
  • Millennium Institute on Immunology and Immunotherapy (CL)
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2022-02-08
Volume
50
Issue
4
Pages
2302-2318
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkac062
PMC
PMC8887480
OpenAlex
W4210307847
Cited by
42
References
0
Citations by year
2026: 5 · 2025: 13 · 2024: 14 · 2023: 5 · 2022: 5
FWCI
3.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Universidad de Chile (submittedVersion, cc-by-nc-nd)
Funders
  • FONDECYT (1160176, 1190156, 1180798, 1211547, 11180621)
  • ANID - ICM (ICN2021_045)
  • CONICYT
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
HIV-1, N6-methyladenosine, epitranscriptomics, Gag protein, RNA demethylation, 5' untranslated region, retroviral replication, RNA methylation
MeSH terms
Adenosine, Methylation, RNA, Viral, Virion, HIV-1, Gene Products, gag, 5' Untranslated Regions

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