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

DOI: 10.1080/15476286.2019.1630797

Authors: Saira Ashraf (Cancer Research UK Nucleic Acid Structure Research Group, The University of Dundee) , Lin Huang (Cancer Research UK Nucleic Acid Structure Research Group, The University of Dundee) , David Lilley (Cancer Research UK Nucleic Acid Structure Research Group, The University of Dundee)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Rna Biology

State: Published (Approved)
Published: June 2019

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.

Journal Keywords: RNA structure; RNA methylation; epigenetic modification; N6-methyladenine; kink-turn; X-ray crystallography

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I03-Macromolecular Crystallography

Added On: 03/07/2019 10:29

Documents:
bnhh44.pdf

Discipline Tags:

Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)