A Second Divalent Metal Ion in the Group II Intron Reaction Center

Peter M. Gordon, Robert Fong, Joseph A. Piccirilli

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Group II introns are mobile genetic elements that have been implicated as agents of genetic diversity, and serve as important model systems for investigating RNA catalysis and pre-mRNA splicing. In the absence of an atomic-resolution structure of the intron, detailed understanding of its catalytic mechanism has remained elusive. Previous identification of a divalent metal ion stabilizing the leaving group in both splicing steps suggested that the group II intron may employ a "two-metal ion" mechanism, a catalytic strategy used by a number of protein phosphoester transfer enzymes. Using metal rescue experiments, we now reveal the presence of a second metal ion required for nucleophile activation in the exon-ligation step of group II intron splicing. Coupled with biochemical and structural evidence of at least two metal ions at the group I intron reaction center, these results suggest a mechanistic paradigm for describing catalysis by large ribozymes.

Original languageEnglish (US)
Pages (from-to)607-612
Number of pages6
JournalChemistry and Biology
Volume14
Issue number6
DOIs
StatePublished - Jun 25 2007
Externally publishedYes

Bibliographical note

Funding Information:
We thank Cecilia Cortez for oligonucleotide synthesis and members of the Piccirilli lab for helpful discussions, advice, and comments regarding the manuscript. P.M.G. and R.F. acknowledge the Medical Scientist Training Program at the University of Chicago (5T32GM007281-32) for support.

Keywords

  • CHEMBIOL
  • RNA

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