Abstract:
: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 II 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 II intron-like tertiary conformation to catalyze splicing.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Fica SM,Mefford MA,Piccirilli JA,Staley JPdoi
10.1038/nsmb.2815subject
Has Abstractpub_date
2014-05-01 00:00:00pages
464-471issue
5eissn
1545-9993issn
1545-9985journal_volume
21pub_type
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