Effect of methylation of adenine N6 on kink turn structure depends on location

Saira Ashraf, Lin Huang, David Lilley (Lead / Corresponding author)

Research output: Contribution to journalArticle

1 Citation (Scopus)
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Abstract

N6-methyladenine is the most common covalent modification in cellular RNA species, with demonstrated functional consequences. At the molecular level this methylation could alter local RNA structure, and/or modulate the binding of specific proteins. We have previously shown that trans-Hoogsteen-sugar (sheared) A:G base pairs can be completely disrupted by methylation, and that this occurs in a sub-set of human box C/D k-turn structures. In this work we have investigated to what extent sequence context affects the severity with which inclusion of N6-methyladenine into different A:G base pairs of a standard k-turn affects RNA folding and L7Ae protein binding. We find that local sequence has a major influence, ranging from complete absence of folding and protein binding to a relatively mild effect. We have determined the crystal structure of one of these species both free and protein-bound, showing the environment of the methyl group and the way the modification is accommodated into the k-turn structure.
Original languageEnglish
Pages (from-to)1377-1385
Number of pages9
JournalRNA Biology
Volume16
Issue number10
Early online date24 Jun 2019
DOIs
Publication statusPublished - 2019

Keywords

  • RNA structure
  • RNA methylation
  • epigenetic modification
  • N6-methyladenine
  • kink-turn
  • X-ray crysallography

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