TY  - JOUR
AU  - Graziadei, Andrea
AU  - Gabel, Frank
AU  - Kirkpatrick, John
AU  - Carlomagno, Teresa
TI  - The guide sRNA sequence determines the activity level of box C/D RNPs
JO  - eLife
VL  - 9
SN  - 2050-084X
CY  - Cambridge
PB  - eLife Sciences Publications
M1  - FZJ-2020-05228
SP  - e50027
PY  - 2020
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.
LB  - PUB:(DE-HGF)16
C6  - 32202498
UR  - <Go to ISI:>//WOS:000521637000001
DO  - DOI:10.7554/eLife.50027
UR  - https://juser.fz-juelich.de/record/888814
ER  -