Epitranscriptomic regulation of HIV-1 full-length RNA packaging.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
28 02 2022
28 02 2022
Historique:
accepted:
25
01
2022
revised:
17
01
2022
received:
13
03
2021
pubmed:
10
2
2022
medline:
16
4
2022
entrez:
9
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35137199
pii: 6524254
doi: 10.1093/nar/gkac062
pmc: PMC8887480
doi:
Substances chimiques
5' Untranslated Regions
0
Gene Products, gag
0
RNA, Viral
0
Adenosine
K72T3FS567
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2302-2318Commentaires et corrections
Type : ErratumIn
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Retrovirology. 2010 Aug 05;7:64
pubmed: 20687923
Curr Protoc Bioinformatics. 2011 Jun;Chapter 2:Unit 2.14
pubmed: 21633945
Science. 2015 May 22;348(6237):917-21
pubmed: 25999508
Elife. 2016 Jul 02;5:
pubmed: 27371828
Front Microbiol. 2018 Mar 28;9:576
pubmed: 29643844
Nat Struct Mol Biol. 2004 Jul;11(7):672-5
pubmed: 15208690
Nucleic Acids Res. 2016 Sep 19;44(16):7922-34
pubmed: 27280976
Sci Rep. 2017 Jul 31;7(1):6902
pubmed: 28761163
Virology. 2006 Jan 20;344(2):391-400
pubmed: 16216294
J Biol Chem. 2004 Nov 12;279(46):48397-403
pubmed: 15355993
J Virol. 1974 Jul;14(1):152-61
pubmed: 4134468
J Virol. 2000 Dec;74(23):11413-7
pubmed: 11070043
FEBS Lett. 2018 Jun;592(12):2012-2022
pubmed: 29754392
Cold Spring Harb Perspect Med. 2012 Feb;2(2):a006916
pubmed: 22355797
Cell. 2014 Nov 20;159(5):1096-1109
pubmed: 25416948
Cell Host Microbe. 2016 Nov 9;20(5):654-665
pubmed: 27773535
Biochemistry. 2005 Jun 28;44(25):9058-66
pubmed: 15966729
RNA Biol. 2020 Apr;17(4):528-538
pubmed: 31918596
Science. 2020 Apr 24;368(6489):413-417
pubmed: 32327595
RNA. 2001 Jan;7(1):143-57
pubmed: 11214176
RNA. 2006 Apr;12(4):542-6
pubmed: 16489186
Nucleic Acids Res. 2011 Nov 1;39(20):8915-27
pubmed: 21791531
Nat Methods. 2014 Sep;11(9):959-65
pubmed: 25028896
Virology. 2014 Apr;454-455:362-70
pubmed: 24530126
Proc Natl Acad Sci U S A. 2020 Mar 17;117(11):6145-6155
pubmed: 32132202
J Virol. 2010 Jul;84(13):6598-604
pubmed: 20427541
Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):13378-13383
pubmed: 27834211
Viruses. 2020 Nov 09;12(11):
pubmed: 33182496
Nucleic Acids Res. 2017 Jun 2;45(10):6051-6063
pubmed: 28334903
Sci Rep. 2015 Dec 03;5:17680
pubmed: 26631448
Cancer Cell. 2019 Apr 15;35(4):677-691.e10
pubmed: 30991027
Nucleic Acids Res. 2015 Jan;43(1):373-84
pubmed: 25452335
J Biol Chem. 2002 May 31;277(22):19967-75
pubmed: 11896057
J Virol. 2002 Apr;76(7):3089-94
pubmed: 11884533
Nucleic Acids Res. 2018 Nov 30;46(21):11539-11552
pubmed: 30239828
J Virol. 1992 Jan;66(1):150-9
pubmed: 1727477
Cell Host Microbe. 2016 May 11;19(5):675-85
pubmed: 27117054
Biochim Biophys Acta. 2016 May;1859(5):719-30
pubmed: 27012366
Nucleic Acids Res. 2016 Jun 2;44(10):e91
pubmed: 26896799
J Biol Chem. 2018 Aug 24;293(34):12992-13005
pubmed: 29976753
Nat Chem Biol. 2014 Feb;10(2):93-5
pubmed: 24316715
J Biol Chem. 2003 Mar 28;278(13):11601-11
pubmed: 12458192
mBio. 2020 Apr 7;11(2):
pubmed: 32265329
J Virol. 1997 May;71(5):3397-406
pubmed: 9094609
Nat Chem Biol. 2011 Oct 16;7(12):885-7
pubmed: 22002720
RNA Biol. 2021 May;18(5):745-758
pubmed: 33103564
Nat Microbiol. 2016 Feb 22;1:16011
pubmed: 27572442
PLoS Biol. 2008 Apr 29;6(4):e96
pubmed: 18447581
Mol Cell. 2013 Jan 10;49(1):18-29
pubmed: 23177736
Virus Res. 2013 Feb;171(2):304-18
pubmed: 23036987
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13033-13038
pubmed: 27791166
Virology. 2016 May;492:204-12
pubmed: 26967976
Nucleic Acids Res. 2007;35(8):2695-704
pubmed: 17426127
J Virol. 2000 Sep;74(18):8307-15
pubmed: 10954529
Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):E201-8
pubmed: 26712001
Nucleic Acids Res. 2013 Jul;41(12):6286-99
pubmed: 23630313
RNA. 2018 Mar;24(3):262-267
pubmed: 29222117
Proc Natl Acad Sci U S A. 1976 Apr;73(4):1154-8
pubmed: 57617
Nature. 2009 Aug 6;460(7256):711-6
pubmed: 19661910
Viruses. 2016 Sep 10;8(9):
pubmed: 27626439
J Virol. 1997 May;71(5):3407-14
pubmed: 9094610
Nat Commun. 2014 Jul 02;5:4304
pubmed: 24986025