Zhou Huiqing, Kimsey Isaac J, Nikolova Evgenia N, Sathyamoorthy Bharathwaj, Grazioli Gianmarc, McSally James, Bai Tianyu, Wunderlich Christoph H, Kreutz Christoph, Andricioaei Ioan, Al-Hashimi Hashim M
Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina, USA.
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California USA.
Nat Struct Mol Biol. 2016 Sep;23(9):803-10. doi: 10.1038/nsmb.3270. Epub 2016 Aug 1.
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.
B-DNA双螺旋能够动态容纳处于沃森-克里克或 hoogsteen 构型的G-C和A-T碱基对。在此，我们表明G-C(+)（其中+表示质子化）和A-U hoogsteen碱基对在A-RNA中极不受青睐。因此，在DNA中作为烷基化损伤形式出现且在RNA中作为转录后修饰出现的N(1)-甲基腺苷和N(1)-甲基鸟苷具有截然不同的后果。虽然它们在双链DNA中形成G-C(+)和A-T hoogsteen碱基对，从而维持双螺旋的结构完整性，但它们会阻碍RNA中的碱基配对并诱导局部双链解链。这些观察结果提供了一种通过转录后修饰破坏RNA结构的机制。B-DNA和A-RNA中形成hoogsteen碱基对的不同倾向可能有助于细胞一方面满足维持基因组稳定性的相反要求，另一方面满足动态调节表观转录组结构的要求。
