m6A minimally impacts the structure, dynamics, and Rev ARM binding properties of HIV-1 RRE stem IIB.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
19
10
2019
accepted:
26
11
2019
entrez:
12
12
2019
pubmed:
12
12
2019
medline:
25
3
2020
Statut:
epublish
Résumé
N6-methyladenosine (m6A) is a ubiquitous RNA post-transcriptional modification found in coding as well as non-coding RNAs. m6A has also been found in viral RNAs where it is proposed to modulate host-pathogen interactions. Two m6A sites have been reported in the HIV-1 Rev response element (RRE) stem IIB, one of which was shown to enhance binding to the viral protein Rev and viral RNA export. However, because these m6A sites have not been observed in other studies mapping m6A in HIV-1 RNA, their significance remains to be firmly established. Here, using optical melting experiments, NMR spectroscopy, and in vitro binding assays, we show that m6A minimally impacts the stability, structure, and dynamics of RRE stem IIB as well as its binding affinity to the Rev arginine-rich-motif (ARM) in vitro. Our results indicate that if present in stem IIB, m6A is unlikely to substantially alter the conformational properties of the RNA. Our results add to a growing view that the impact of m6A on RNA depends on sequence context and Mg2+.
Identifiants
pubmed: 31825959
doi: 10.1371/journal.pone.0224850
pii: PONE-D-19-28951
pmc: PMC6905585
doi:
Substances chimiques
RNA, Viral
0
rev Gene Products, Human Immunodeficiency Virus
0
N-methyladenosine
CLE6G00625
Adenosine
K72T3FS567
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0224850Subventions
Organisme : NIAID NIH HHS
ID : U54 AI150470
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM103297
Pays : United States
Déclaration de conflit d'intérêts
H.M.A. is an advisor and holds an ownership interest in Nymirum Inc., an RNA- based drug discovery company. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Références
Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7366-70
pubmed: 1871141
Cell. 1991 Apr 19;65(2):241-8
pubmed: 2015625
PLoS Pathog. 2018 Apr 16;14(4):e1006995
pubmed: 29659627
Cell. 2015 Jun 4;161(6):1388-99
pubmed: 26046440
J Am Chem Soc. 2015 Feb 11;137(5):2107-15
pubmed: 25611135
Proc Natl Acad Sci U S A. 1974 Oct;71(10):3971-5
pubmed: 4372599
Cell Rep. 2020 Feb 25;30(8):2472-2480.e4
pubmed: 32101729
RNA. 2007 Feb;13(2):251-66
pubmed: 17194721
Cell Host Microbe. 2016 May 11;19(5):675-85
pubmed: 27117054
Biochemistry. 2007 Jan 9;46(1):172-81
pubmed: 17198387
Nucleic Acids Res. 2019 Jul 26;47(13):7105-7117
pubmed: 31199872
Cell. 2017 Jun 15;169(7):1187-1200
pubmed: 28622506
Biochemistry. 1994 Mar 15;33(10):2741-7
pubmed: 8130185
Chem Rev. 2006 May;106(5):1700-19
pubmed: 16683750
Science. 1996 Sep 13;273(5281):1547-51
pubmed: 8703216
Annu Rev Biophys Biomol Struct. 2005;34:221-43
pubmed: 15869389
Nat Commun. 2018 Jul 17;9(1):2761
pubmed: 30018356
Biochemistry. 1994 May 10;33(18):5357-66
pubmed: 8180157
Cell Host Microbe. 2016 Nov 9;20(5):654-665
pubmed: 27773535
Proc Natl Acad Sci U S A. 2000 May 9;97(10):5107-12
pubmed: 10792052
EMBO Rep. 2017 Sep;18(9):1631-1645
pubmed: 28623187
Elife. 2016 Jul 02;5:
pubmed: 27371828
EMBO J. 1992 Mar;11(3):1119-29
pubmed: 1547776
Mol Cell. 2008 Sep 26;31(6):824-34
pubmed: 18922466
Nature. 2015 Mar 26;519(7544):486-90
pubmed: 25799993
Elife. 2014 Aug 27;3:e03656
pubmed: 25163983
Cell Stem Cell. 2015 Mar 5;16(3):289-301
pubmed: 25683224
Chemistry. 2015 Aug 10;21(33):11634-11643
pubmed: 26237536
Mol Cell. 2016 Feb 18;61(4):507-519
pubmed: 26876937
J Virol. 1991 Apr;65(4):2131-4
pubmed: 2002556
Neuron. 2018 Jan 17;97(2):313-325.e6
pubmed: 29346752
Nat Rev Mol Cell Biol. 2017 Jan;18(1):31-42
pubmed: 27808276
J Biomol NMR. 1995 Nov;6(3):277-93
pubmed: 8520220
Nucleic Acids Res. 2003 Aug 1;31(15):4472-80
pubmed: 12888507
Cell Host Microbe. 2016 Nov 9;20(5):666-673
pubmed: 27773536
Prog Nucl Magn Reson Spectrosc. 2019 Jun - Aug;112-113:55-102
pubmed: 31481159
Nat Methods. 2016 Dec 29;14(1):23-31
pubmed: 28032622
Cell Res. 2014 Dec;24(12):1403-19
pubmed: 25412662
Nat Microbiol. 2016 Feb 22;1:16011
pubmed: 27572442
J Mol Biol. 2000 Jan 28;295(4):711-7
pubmed: 10656783
Nature. 2012 Apr 29;485(7397):201-6
pubmed: 22575960
Curr Opin Genet Dev. 2018 Feb;48:1-7
pubmed: 29040886
Cell. 2012 Jun 22;149(7):1635-46
pubmed: 22608085
Cell. 1990 Feb 23;60(4):675-83
pubmed: 2406030
Elife. 2014 Dec 08;3:e04120
pubmed: 25486594
Cell. 1991 Nov 1;67(3):529-36
pubmed: 1934059
Biopolymers. 2003 Sep;70(1):103-19
pubmed: 12925996
Cell. 2013 Oct 24;155(3):594-605
pubmed: 24243017
Nature. 2015 Feb 26;518(7540):560-4
pubmed: 25719671
Nature. 2014 Jan 2;505(7481):117-20
pubmed: 24284625
Nature. 1989 Mar 16;338(6212):254-7
pubmed: 2784194
Annu Rev Cell Dev Biol. 2017 Oct 6;33:319-342
pubmed: 28759256
J Am Chem Soc. 2005 Jan 19;127(2):713-21
pubmed: 15643897