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Updated: Jan 23, 2026
DNAzyme-dependent Analysis of rRNA 2’-O-Methylation
Published on: September 16, 2019
Effect of methylation of adenine N6 on kink turn structure depends on location
Saira Ashraf1, Lin Huang1, David M J Lilley1
1Cancer Research UK Nucleic Acid Structure Research Group, MSI/WTB Complex, The University of Dundee , Dundee , U.K.
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 ofD/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.
Insights
N6-methyladenine (m6A) is a common RNA modification. Its impact on RNA structure and protein binding depends heavily on the surrounding RNA sequence context within k-turn structures.
Area of Science:
- Molecular Biology
- Biochemistry
- Structural Biology
Background:
- N6-methyladenine (m6A) is the most prevalent RNA modification.
- m6A can influence RNA structure and protein interactions.
- Previous work showed m6A disrupts specific A:G base pairs in k-turn structures.
Purpose of the Study:
- Investigate how sequence context affects m6A's impact on A:G base pairs in k-turns.
- Determine the effect of sequence context on RNA folding and L7Ae protein binding in the presence of m6A.
Main Methods:
- Studied m6A incorporation into various A:G base pairs within standard k-turn structures.
- Assessed RNA folding and L7Ae protein binding.
- Determined crystal structures of modified RNA free and bound to L7Ae protein.
Main Results:
- Local sequence context significantly influences the effects of m6A.
- Effects ranged from complete disruption of folding and binding to mild alterations.
- Crystal structures revealed the methyl group's environment and its accommodation within the k-turn.
Conclusions:
- Sequence context is a critical determinant of m6A's functional consequences in k-turn structures.
- m6A's impact on RNA folding and protein binding is context-dependent.
- Structural insights explain how m6A is accommodated and influences RNA-protein interactions.
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