title: m(1)A and m(1)G disrupt A-RNA structure through the intrinsic instability of Hoogsteen base pairs.
abstract: The B-DNA double helix can dynamically accommodate G-C and A-T base pairs in either Watson-Crick or Hoogsteen configurations. Here, we show that G-C(+) (in which + indicates protonation) and A-U Hoogsteen base pairs are strongly disfavored in A-RNA. As a result,N(1)-methyladenosine and N(1)-methylguanosine, which occur in DNA as a form of alkylation damage and in RNA as post-transcriptional modifications, have dramatically different consequences. Whereas they create G-C(+) and A-T Hoogsteen base pairs in duplex DNA, thereby maintaining the structural integrity of the double helix, they block base-pairing and induce local duplex melting in RNA. These observations provide a mechanism for disrupting RNA structure through post-transcriptional modifications. The different propensities to form Hoogsteen base pairs in B-DNA and A-RNA may help cells meet the opposing requirements of maintaining genome stability, on the one hand, and of dynamically modulating the structure of the epitranscriptome, on the other.
authors.affiliation: Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Isaac J
authors.initials: IJ
authors.lastname: Kimsey
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, California USA.
authors.forename: Evgenia N
authors.initials: EN
authors.lastname: Nikolova
authors.affiliation: Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Bharathwaj
authors.initials: B
authors.lastname: Sathyamoorthy
authors.affiliation: Department of Chemistry, University of California Irvine, Irvine, California USA.
authors.forename: Gianmarc
authors.initials: G
authors.lastname: Grazioli
authors.affiliation: Department of Chemistry, University of California Irvine, Irvine, California USA.
authors.forename: James
authors.initials: J
authors.lastname: McSally
authors.affiliation: Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina, USA.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Bai
authors.affiliation: Bachem Americas, Torrance, California USA.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Wunderlich
authors.affiliation: Institute of Organic Chemistry, University of Innsbruck, Innsbruck, Austria.|Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kreutz
authors.affiliation: Department of Chemistry, University of California Irvine, Irvine, California USA.
authors.forename: Ioan
authors.initials: I
authors.lastname: Andricioaei
authors.affiliation: Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina, USA.|Department of Chemistry, Duke University, Durham, North Carolina, USA.
authors.forename: Hashim M
authors.initials: HM
authors.lastname: Al-Hashimi
mesh_terms: D000241:Adenosine / Q000737:chemistry; D020029:Base Pairing; D001483:Base Sequence; D006151:Guanosine / Q000737:chemistry; D006860:Hydrogen Bonding; D055029:Inverted Repeat Sequences; D008958:Models, Molecular; D012313:RNA / Q000737:chemistry*; D020871:RNA Stability; D012330:RNA, Double-Stranded / Q000737:chemistry*
chemical_list: D012330:RNA, Double-Stranded; D006151:Guanosine; D012313:RNA; D000241:Adenosine