A conformational switch in PRP8 mediates metal ion coordination that promotes pre-mRNA exon ligation

Matthew J. Schellenberg, Tao Wu, Dustin B. Ritchie, Sebastian Fica, Jonathan P. Staley, Karim A. Atta, Paul Lapointe, Andrew M. Macmillan

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Splicing of pre-mRNAs in eukaryotes is catalyzed by the spliceosome, a large RNA-protein metalloenzyme. The catalytic center of the spliceosome involves a structure comprising the U2 and U6 snRNAs and includes a metal bound by U6 snRNA. The precise architecture of the splicesome active site, however, and the question of whether it includes protein components, remains unresolved. A wealth of evidence places the protein PRP8 at the heart of the spliceosome through assembly and catalysis. Here we provide evidence that the RNase H domain of PRP8 undergoes a conformational switch between the two steps of splicing, rationalizing yeast prp8 alleles that promote either the first or second step. We also show that this switch unmasks a metal-binding site involved in the second step. Together, these data establish that PRP8 is a metalloprotein that promotes exon ligation within the spliceosome.

Original languageEnglish (US)
Pages (from-to)728-734
Number of pages7
JournalNature Structural and Molecular Biology
Volume20
Issue number6
DOIs
StatePublished - Jun 2013

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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