Details
| Original language | English |
|---|---|
| Article number | e50027 |
| Journal | ELIFE |
| Volume | 9 |
| Publication status | Published - 23 Mar 2020 |
Abstract
2’-O-rRNA methylation, which is essential in eukaryotes and archaea, is catalysed by the Box C/D RNP complex in an RNA-guided manner. Despite the conservation of the methylation sites, the abundance of site-specific modifications shows variability across species and tissues, suggesting that rRNA methylation may provide a means of controlling gene expression. As all Box C/D RNPs are thought to adopt a similar structure, it remains unclear how the methylation efficiency is regulated. Here, we provide the first structural evidence that, in the context of the Box C/D RNP, the affinity of the catalytic module fibrillarin for the substrate–guide helix is dependent on the RNA sequence outside the methylation site, thus providing a mechanism by which both the substrate and guide RNA sequences determine the degree of methylation. To reach this result, we develop an iterative structure-calculation protocol that exploits the power of integrative structural biology to characterize conformational ensembles.
ASJC Scopus subject areas
- Neuroscience(all)
- General Neuroscience
- Immunology and Microbiology(all)
- General Immunology and Microbiology
- Biochemistry, Genetics and Molecular Biology(all)
- General Biochemistry,Genetics and Molecular Biology
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In: ELIFE, Vol. 9, e50027, 23.03.2020.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - The guide sRNA sequence determines the activity level of BOX C/D RNPs
AU - Graziadei, Andrea
AU - Gabel, Frank
AU - Kirkpatrick, John
AU - Carlomagno, Teresa
N1 - Funding Information: Funder Grant reference number Author European Commission FP7 ITN project RNPnet(contract number 289007 Andrea Graziadei Deutsche Forschungsgemeinschaft CA294/3-2 Teresa Carlomagno.
PY - 2020/3/23
Y1 - 2020/3/23
N2 - 2’-O-rRNA methylation, which is essential in eukaryotes and archaea, is catalysed by the Box C/D RNP complex in an RNA-guided manner. Despite the conservation of the methylation sites, the abundance of site-specific modifications shows variability across species and tissues, suggesting that rRNA methylation may provide a means of controlling gene expression. As all Box C/D RNPs are thought to adopt a similar structure, it remains unclear how the methylation efficiency is regulated. Here, we provide the first structural evidence that, in the context of the Box C/D RNP, the affinity of the catalytic module fibrillarin for the substrate–guide helix is dependent on the RNA sequence outside the methylation site, thus providing a mechanism by which both the substrate and guide RNA sequences determine the degree of methylation. To reach this result, we develop an iterative structure-calculation protocol that exploits the power of integrative structural biology to characterize conformational ensembles.
AB - 2’-O-rRNA methylation, which is essential in eukaryotes and archaea, is catalysed by the Box C/D RNP complex in an RNA-guided manner. Despite the conservation of the methylation sites, the abundance of site-specific modifications shows variability across species and tissues, suggesting that rRNA methylation may provide a means of controlling gene expression. As all Box C/D RNPs are thought to adopt a similar structure, it remains unclear how the methylation efficiency is regulated. Here, we provide the first structural evidence that, in the context of the Box C/D RNP, the affinity of the catalytic module fibrillarin for the substrate–guide helix is dependent on the RNA sequence outside the methylation site, thus providing a mechanism by which both the substrate and guide RNA sequences determine the degree of methylation. To reach this result, we develop an iterative structure-calculation protocol that exploits the power of integrative structural biology to characterize conformational ensembles.
UR - http://www.scopus.com/inward/record.url?scp=85082342240&partnerID=8YFLogxK
U2 - 10.7554/eLife.50027
DO - 10.7554/eLife.50027
M3 - Article
C2 - 32202498
AN - SCOPUS:85082342240
VL - 9
JO - ELIFE
JF - ELIFE
SN - 2050-084X
M1 - e50027
ER -