Visualizing Group II Intron Catalysis Through the Stages of Splicing

Cell. 2012 Oct 26;151(3):497-507. doi: 10.1016/j.cell.2012.09.033.

Abstract

Group II introns are self-splicing ribozymes that share a reaction mechanism and a common ancestor with the eukaryotic spliceosome, thereby providing a model system for understanding the chemistry of pre-mRNA splicing. Here we report 14 crystal structures of a group II intron at different stages of catalysis. We provide a detailed mechanism for the first step of splicing, we describe a reversible conformational change between the first and the second steps of splicing, and we present the ligand-free intron structure after splicing in an active state that corresponds to the retrotransposable form of the intron. During each reaction, the reactants are aligned and activated by a heteronuclear four-metal-ion center that contains a metal cluster and obligate monovalent cations, and they adopt a structural arrangement similar to that of protein endonucleases. Based on our data, we propose a model for the splicing cycle and show that it is applicable to the eukaryotic spliceosome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillaceae / genetics*
  • Catalytic Domain
  • Crystallography, X-Ray
  • Introns*
  • Models, Biological*
  • Mutation
  • RNA Precursors / chemistry
  • RNA Precursors / metabolism
  • RNA Splice Sites
  • RNA Splicing*
  • RNA, Bacterial / chemistry*
  • RNA, Bacterial / metabolism
  • Retroelements

Substances

  • RNA Precursors
  • RNA Splice Sites
  • RNA, Bacterial
  • Retroelements

Associated data

  • PDB/4E8K
  • PDB/4E8M
  • PDB/4E8N
  • PDB/4E8P
  • PDB/4E8Q
  • PDB/4E8R
  • PDB/4E8T
  • PDB/4E8V
  • PDB/4FAQ
  • PDB/4FAR
  • PDB/4FAU
  • PDB/4FAW
  • PDB/4FAX
  • PDB/4FB0