Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 21, Issue 5, Pages 464-471Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.2815
Keywords
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Funding
- US National Institutes of Health training [T32 GM007183]
- US National Institutes of Health [R01GM088656]
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To catalyze pre-mRNA splicing, U6 small nuclear RNA positions two metals that interact directly with the scissile phosphates. U6 metal ligands correspond stereospecifically to metal ligands within the catalytic domain V of a group 11 self-splicing intron. Domain V ligands are organized by base-triple interactions, which also juxtapose the 3' splice site with the catalytic metals. However, in the spliceosome, the mechanism for organizing catalytic metals and recruiting the substrate has remained unclear. Here we show by genetics, cross-linking and biochemistry in yeast that analogous triples form in U6 and promote catalytic-metal binding and both chemical steps of splicing. Because the triples include an element that defines the 5' splice site, they also provide a mechanism for juxtaposing the pre-mRNA substrate with the catalytic metals. Our data indicate that U6 adopts a group 11 intron-like tertiary conformation to catalyze splicing.
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