m(1)A and m(1)G disrupt A-RNA structure through the intrinsic instability of Hoogsteen base pairs.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhou, H; Kimsey, IJ; Nikolova, EN; Sathyamoorthy, B; Grazioli, G; McSally, J; Bai, T; Wunderlich, CH; Kreutz, C; Andricioaei, I; Al-Hashimi, HM

Published Date

  • September 2016

Published In

Volume / Issue

  • 23 / 9

Start / End Page

  • 803 - 810

PubMed ID

  • 27478929

Pubmed Central ID

  • 27478929

Electronic International Standard Serial Number (EISSN)

  • 1545-9985

International Standard Serial Number (ISSN)

  • 1545-9993

Digital Object Identifier (DOI)

  • 10.1038/nsmb.3270

Language

  • eng