Key result
Mutations in conserved sequence elements of the sRNA severely interfere with the catalytic activity of box C/D sRNPs and prevent formation of the di-sRNP.
The study provides structural evidence that the di-sRNP architecture is functionally relevant and required for the catalytic activity of 2'-O-ribose methylation.
Supports di-sRNP as essential for box C/D catalysis; leaves open validation in mammalian disease models.
In all three kingdoms of life, nucleotides in ribosomal RNA (rRNA) are post-transcriptionally modified. One type of chemical modification is 2'-O-ribose methylation, which is, in eukaryotes and archaea, performed by box C/D small ribonucleoproteins (box C/D sRNPs in archaea) and box C/D small nucleolar ribonucleoproteins (box C/D snoRNPs in eukaryotes), respectively. Recently, the first structure of any catalytically active box C/D s(no)RNP determined by electron microscopy and single particle analysis surprisingly demonstrated that they are dimeric RNPs. Mutational analyses of the Nop5 protein interface suggested that di-sRNP formation is also required for the in vitro catalytic activity. We have now analyzed the functional relevance of the second interface, the sRNA interface, within the box C/D di-sRNP. Mutations in conserved sequence elements of the sRNA, which allow sRNP assembly but which severely interfere with the catalytic activity of box C/D sRNPs, prevent formation of the di-sRNP. In addition, we can observe the dimeric box C/D sRNP architecture with a different box C/D sRNP, suggesting that this architecture is conserved. Together, these results provide further support for the functional relevance of the di-sRNP architecture and also provide a structural explanation for the observed defects in catalysis of 2'-O-ribose methylation.
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Bleichert et al. (2010) studied this question. Mutations in conserved sequence elements of the sRNA was evaluated on di-sRNP formation and catalytic activity. Mutations in conserved sequence elements of the sRNA severely interfere with the catalytic activity of box C/D sRNPs and prevent formation of the di-sRNP.
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