Article ; Online: Epitranscriptomic regulation of HIV-1 full-length RNA packaging.
2022 Volume 50, Issue 4, Page(s) 2302–2318
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 ... ...
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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MeSH term(s) | 5' Untranslated Regions ; Adenosine/genetics ; Adenosine/metabolism ; Gene Products, gag/genetics ; HIV-1/metabolism ; Methylation ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Virion/metabolism |
Chemical Substances | 5' Untranslated Regions ; Gene Products, gag ; RNA, Viral ; Adenosine (K72T3FS567) |
Language | English |
Publishing date | 2022-02-07 |
Publishing country | England |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 186809-3 |
ISSN | 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048 |
ISSN (online) | 1362-4962 ; 1362-4954 |
ISSN | 0301-5610 ; 0305-1048 |
DOI | 10.1093/nar/gkac062 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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