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000888814 1001_ $$00000-0001-7709-6002$$aGraziadei, Andrea$$b0
000888814 245__ $$aThe guide sRNA sequence determines the activity level of box C/D RNPs
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000888814 520__ $$a2’-O-rRNA methylation, which is essential in eukaryotes and archaea, is catalysed by the Box C/D RNP complex in an RNA-guided manner. Despite the conservation of the methylation sites, the abundance of site-specific modifications shows variability across species and tissues, suggesting that rRNA methylation may provide a means of controlling gene expression. As all Box C/D RNPs are thought to adopt a similar structure, it remains unclear how the methylation efficiency is regulated. Here, we provide the first structural evidence that, in the context of the Box C/D RNP, the affinity of the catalytic module fibrillarin for the substrate–guide helix is dependent on the RNA sequence outside the methylation site, thus providing a mechanism by which both the substrate and guide RNA sequences determine the degree of methylation. To reach this result, we develop an iterative structure-calculation protocol that exploits the power of integrative structural biology to characterize conformational ensembles.
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000888814 7001_ $$0P:(DE-HGF)0$$aGabel, Frank$$b1
000888814 7001_ $$0P:(DE-HGF)0$$aKirkpatrick, John$$b2
000888814 7001_ $$00000-0002-2437-2760$$aCarlomagno, Teresa$$b3$$eCorresponding author
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