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Control of box C/D snoRNP assembly by N 6 -methylation of adenine

DOI: 10.15252/embr.201743967 DOI Help

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

Type: Journal Paper
Journal: Embo Reports

State: Published (Approved)
Published: June 2017
Diamond Proposal Number(s): 10071 , 8268

Open Access Open Access

Abstract: N6-methyladenine is the most widespread mRNA modification. A subset of human box C/D snoRNA species have target GAC sequences that lead to formation of N6-methyladenine at a key trans Hoogsteen-sugar A·G base pair, of which half are methylated in vivo. The GAC target is conserved only in those that are methylated. Methylation prevents binding of the 15.5-kDa protein and the induced folding of the RNA. Thus, the assembly of the box C/D snoRNP could in principle be regulated by RNA methylation at its critical first stage. Crystallography reveals that N6-methylation of adenine prevents the formation of trans Hoogsteen-sugar A·G base pairs, explaining why the box C/D RNA cannot adopt its kinked conformation. More generally, our data indicate that sheared A·G base pairs (but not Watson–Crick base pairs) are more susceptible to disruption by N6mA methylation and are therefore possible regulatory sites. The human signal recognition particle RNA and many related Alu retrotransposon RNA species are also methylated at N6 of an adenine that forms a sheared base pair with guanine and mediates a key tertiary interaction.

Journal Keywords: epigenetics; G·A base pairs; k-turn; RNA methylation; signal recognition particle

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography

Documents:
Huang_et_al-2017-EMBO_reports.pdf