Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1473-1671 |
| Number of pages | 15 |
| Journal | EMBO Reports |
| Volume | 18 |
| Issue number | 9 |
| Early online date | 16 Jun 2017 |
| DOIs | |
| Publication status | Published - 1 Sep 2017 |
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Keywords
- RNA methylation
- epigenetics
- G•A basepairs
- k-turn
- signal recognition particle
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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 journal › Article
TY - JOUR
T1 - Control of box C/D snoRNP assembly by N6-methylation of adenine
AU - Huang, Lin
AU - Ashraf, Saira
AU - Wang, Jia
AU - Lilley, David M. J.
N1 - Cancer Research UK program grant A18604.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
KW - RNA methylation
KW - epigenetics
KW - G•A basepairs
KW - k-turn
KW - signal recognition particle
U2 - 10.15252/embr.201743967
DO - 10.15252/embr.201743967
M3 - Article
C2 - 28623187
VL - 18
SP - 1473
EP - 1671
JO - EMBO Reports
JF - EMBO Reports
SN - 1469-221X
IS - 9
ER -