Structural organization of box C/D RNA-guided RNA methyltransferase

Keqiong Ye, Ru Jia, Jinzhong Lin, Minghua Ju, Jin Peng, Anbi Xu, Liman Zhang

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Box C/D guide RNAs are abundant noncoding RNAs that primarily function to direct the 2′-O-methylation of specific nucleotides by base-pairing with substrate RNAs. In archaea, a bipartite C/D RNA assembles with L7Ae, Nop5, and the methyltransferase fibrillarin into a modification enzyme with unique substrate specificity. Here, we determined the crystal structure of an archaeal C/D RNA - protein complex (RNP) composed of all 3 core proteins and an engineered half-guide RNA at 4 Å resolution, as well as 2 protein substructures at higher resolution. The RNP structure reveals that the C-terminal domains of Nop5 in the dimeric complex provide symmetric anchoring sites for 2 L7Ae-associated kink-turn motifs of the C/D RNA. A prominent protrusion in Nop5 seems to be important for guide RNA organization and function and for discriminating the structurally related U4 snRNA. Multiple conformations of the N-terminal domain of Nop5 and its associated fibrillarin in different structures indicate the inherent flexibility of the catalytic module, suggesting that a swinging motion of the catalytic module is part of the enzyme mechanism. We also built a model of a native C/D RNP with substrate and fibrillarin in an active conformation. Our results provide insight into the overall organization and mechanism of action of C/D RNA - guided RNA methyltransferases.

Original languageEnglish (US)
Pages (from-to)13808-13813
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number33
DOIs
StatePublished - Aug 18 2009
Externally publishedYes

Keywords

  • Crystal structure
  • Methylation
  • Non-coding RNA
  • RNA-protein complex

ASJC Scopus subject areas

  • General

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