Control of box C/D snoRNP assembly by N6-methylation of adenine

Lin Huang, Saira Ashraf, Jia Wang, David M. J. Lilley (Lead / Corresponding author)

Research output: Contribution to journalArticle

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Abstract

N6-methyladenine is the most widespread mRNA modification. A sub-set 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 basepair, 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 basepairs, explaining why the box C/D RNA cannot adopt its kinked conformation. More generally, our data indicate that sheared A•G basepairs (but not Watson-Crick basepairs) 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 basepair with guanine and mediates a key tertiary interaction.
Original languageEnglish
Pages (from-to)1473-1671
Number of pages15
JournalEMBO Reports
Volume18
Issue number9
Early online date16 Jun 2017
DOIs
Publication statusPublished - 1 Sep 2017

Fingerprint

Small Nucleolar Ribonucleoproteins
Methylation
Adenine
RNA
Sugars
Signal Recognition Particle
Small Nucleolar RNA
Retroelements
Crystallography
Protein Folding
Guanine
Conformations
Messenger RNA
Proteins

Keywords

  • RNA methylation
  • epigenetics
  • G•A basepairs
  • k-turn
  • signal recognition particle

Cite this

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title = "Control of box C/D snoRNP assembly by N6-methylation of adenine",
abstract = "N6-methyladenine is the most widespread mRNA modification. A sub-set 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 basepair, 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 basepairs, explaining why the box C/D RNA cannot adopt its kinked conformation. More generally, our data indicate that sheared A•G basepairs (but not Watson-Crick basepairs) 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 basepair with guanine and mediates a key tertiary interaction.",
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Control of box C/D snoRNP assembly by N6-methylation of adenine. / Huang, Lin; Ashraf, Saira; Wang, Jia; Lilley, David M. J. (Lead / Corresponding author).

In: EMBO Reports, Vol. 18, No. 9, 01.09.2017, p. 1473-1671.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Control of box C/D snoRNP assembly by N6-methylation of adenine

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AU - Ashraf, Saira

AU - Wang, Jia

AU - Lilley, David M. J.

N1 - Cancer Research UK program grant A18604.

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