Impact of 3-deazapurine nucleobases on RNA properties.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
07 05 2021
07 05 2021
Historique:
accepted:
29
03
2021
received:
05
03
2021
pubmed:
16
4
2021
medline:
29
5
2021
entrez:
15
4
2021
Statut:
ppublish
Résumé
Deazapurine nucleosides such as 3-deazaadenosine (c3A) are crucial for atomic mutagenesis studies of functional RNAs. They were the key for our current mechanistic understanding of ribosomal peptide bond formation and of phosphodiester cleavage in recently discovered small ribozymes, such as twister and pistol RNAs. Here, we present a comprehensive study on the impact of c3A and the thus far underinvestigated 3-deazaguanosine (c3G) on RNA properties. We found that these nucleosides can decrease thermodynamic stability of base pairing to a significant extent. The effects are much more pronounced for 3-deazapurine nucleosides compared to their constitutional isomers of 7-deazapurine nucleosides (c7G, c7A). We furthermore investigated base pair opening dynamics by solution NMR spectroscopy and revealed significantly enhanced imino proton exchange rates. Additionally, we solved the X-ray structure of a c3A-modified RNA and visualized the hydration pattern of the minor groove. Importantly, the characteristic water molecule that is hydrogen-bonded to the purine N3 atom and always observed in a natural double helix is lacking in the 3-deazapurine-modified counterpart. Both, the findings by NMR and X-ray crystallographic methods hence provide a rationale for the reduced pairing strength. Taken together, our comparative study is a first major step towards a comprehensive understanding of this important class of nucleoside modifications.
Identifiants
pubmed: 33856457
pii: 6226676
doi: 10.1093/nar/gkab256
pmc: PMC8096147
doi:
Substances chimiques
7-deazapurine
0
Purines
0
3-deazaadenosine
037V4520IY
RNA
63231-63-0
Tubercidin
M351LCX45Y
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4281-4293Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
Nucleic Acids Res. 2008 May;36(9):2981-9
pubmed: 18388130
J Phys Chem B. 2010 Jun 10;114(22):7656-61
pubmed: 20469878
Chem Sci. 2016 Feb 1;7(2):995-1010
pubmed: 29896368
Chemistry. 2018 Dec 17;24(71):18903-18906
pubmed: 30300940
Nucleic Acids Res. 2020 Dec 2;48(21):12394-12406
pubmed: 33170270
J Am Chem Soc. 2006 Apr 5;128(13):4453-9
pubmed: 16569023
Biopolymers. 2001-2002;61(1):3-31
pubmed: 11891626
Nat Struct Mol Biol. 2014 Sep;21(9):787-93
pubmed: 25132179
Chem Biol. 2008 May;15(5):485-92
pubmed: 18439847
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):22-5
pubmed: 20057045
Angew Chem Int Ed Engl. 2017 Dec 11;56(50):15954-15958
pubmed: 29098759
Wiley Interdiscip Rev RNA. 2017 May;8(3):
pubmed: 27863022
J Org Chem. 2018 Aug 3;83(15):8589-8595
pubmed: 29911384
Chimia (Aarau). 2013;67(5):322-6
pubmed: 23863265
RNA. 2016 Jun;22(6):934-42
pubmed: 27099368
Nucleic Acids Res. 2009 Dec;37(22):7728-40
pubmed: 19843610
Nature. 2020 Nov;587(7835):663-667
pubmed: 33116304
Biopolymers. 1987 Sep;26(9):1601-20
pubmed: 3663875
Nucleic Acids Res. 2017 Jul 27;45(13):8014-8025
pubmed: 28549193
Nucleic Acids Res. 1993 Apr 25;21(8):1743-6
pubmed: 8493091
Beilstein J Org Chem. 2016 Nov 28;12:2556-2562
pubmed: 28144324
J Am Chem Soc. 2007 Feb 7;129(5):1026-7
pubmed: 17263372
Chembiochem. 2008 Feb 15;9(3):464-70
pubmed: 18219644
Bioorg Med Chem. 2018 Jan 1;26(1):77-83
pubmed: 29174509
Nucleic Acids Res. 1998 Feb 15;26(4):1010-8
pubmed: 9461461
Nucleic Acids Res. 1990 Aug 25;18(16):4771-8
pubmed: 2395641
RNA. 2009 Apr;15(4):707-15
pubmed: 19228585
Proc Natl Acad Sci U S A. 2019 May 28;116(22):10783-10791
pubmed: 31088965
J Mol Biol. 1999 Sep 17;292(2):275-87
pubmed: 10493875
Nat Struct Biol. 1996 Jan;3(1):24-31
pubmed: 8548450
Biochemistry. 1983 Jan 18;22(2):256-63
pubmed: 6824629
Acc Chem Res. 2014 Apr 15;47(4):1446-54
pubmed: 24702131
Nat Protoc. 2011 May;6(5):580-92
pubmed: 21527916
Nucleic Acids Res. 2007;35(18):6181-95
pubmed: 17855404
Biochemistry. 2009 Aug 25;48(33):7777-9
pubmed: 19634899
Chemistry. 2011 Jul 11;17(29):8156-64
pubmed: 21626581
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):133-44
pubmed: 20124693
Nucleic Acids Res. 2005 Mar 14;33(5):1618-27
pubmed: 15767286
Nucleic Acids Res. 2019 Aug 22;47(14):7223-7234
pubmed: 31276590
RNA. 2012 Jun;18(6):1222-9
pubmed: 22543863
Nucleic Acids Res. 1992 Jul 11;20(13):2297-306
pubmed: 1630898
Methods Enzymol. 1995;261:383-413
pubmed: 8569504
Chem Soc Rev. 2020 Oct 21;49(20):7331-7353
pubmed: 32944725
Proc Natl Acad Sci U S A. 2018 Jan 16;115(3):E382-E389
pubmed: 29298914
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Acc Chem Res. 2012 Dec 18;45(12):2035-44
pubmed: 22533519
Angew Chem Int Ed Engl. 2002 Jul 2;41(13):2265-9
pubmed: 12203559
Nat Chem Biol. 2005 Jun;1(1):45-52
pubmed: 16407993
Med Res Rev. 2017 Nov;37(6):1429-1460
pubmed: 28834581
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):352-67
pubmed: 22505256
Org Biomol Chem. 2016 Apr 28;14(16):3934-42
pubmed: 27044927
J Phys Chem B. 2011 Dec 1;115(47):13925-34
pubmed: 22059929
Angew Chem Int Ed Engl. 2020 Feb 10;59(7):2837-2843
pubmed: 31804735
J Am Chem Soc. 2009 Sep 2;131(34):12068-9
pubmed: 19663509
ChemMedChem. 2013 Jun;8(6):985-93
pubmed: 23606629
J Biomol NMR. 1998 Feb;11(2):221-6
pubmed: 9679296
J Am Chem Soc. 2009 May 6;131(17):6093-5
pubmed: 19354216
Acc Chem Res. 2009 Jan 20;42(1):33-44
pubmed: 18921985
J Am Chem Soc. 2004 Aug 11;126(31):9532-3
pubmed: 15291544
Org Lett. 2019 Jun 7;21(11):3900-3903
pubmed: 31081638
Angew Chem Int Ed Engl. 2015 Dec 7;54(50):15128-15133
pubmed: 26473980
J Am Chem Soc. 2004 Mar 10;126(9):2862-9
pubmed: 14995203
Nucleic Acids Res. 2006;34(16):4324-34
pubmed: 16936323
Methods Enzymol. 2014;549:189-219
pubmed: 25432750