%0 Journal Article
%A Graziadei, Andrea
%A Gabel, Frank
%A Kirkpatrick, John
%A Carlomagno, Teresa
%T The guide sRNA sequence determines the activity level of box C/D RNPs
%J eLife
%V 9
%@ 2050-084X
%C Cambridge
%I eLife Sciences Publications
%M FZJ-2020-05228
%P e50027
%D 2020
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 32202498
%U <Go to ISI:>//WOS:000521637000001
%R 10.7554/eLife.50027
%U https://juser.fz-juelich.de/record/888814