Molecular modelling of the GIR1 branching ribozyme gives new insight into evolution of structurally related ribozymes

• Bertrand Beckert ^[4] ; Henrik Nielsen ^[1] ; Christer Einvik ^[2] ; Steinar D Johansen ^[3] ; Eric Westhof ^[4] ; Benoît Masquida ^[4]
  1. [1] University of Copenhagen

     University of Copenhagen

     Dinamarca

     
  2. [2] University Hospital of North Norway

     University Hospital of North Norway

     Noruega

     
  3. [3] The Arctic University of Norway

     The Arctic University of Norway

     Noruega

     
  4. [4] Architecture et Réactivité de l'ARN, Université Louis Pasteur de Strasbourg, IBMC, CNRS, Strasbourg, France

  Mostrar afiliaciones +
• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 27, Nº. 4, 2008, págs. 667-678
• Idioma: inglés
• Enlaces
  • Texto completo
• Resumen

  • Twin-ribozyme introns contain a branching ribozyme (GIR1) followed by a homing endonuclease (HE) encoding sequence embedded in a peripheral domain of a group I splicing ribozyme (GIR2). GIR1 catalyses the formation of a lariat with 3 nt in the loop, which caps the HE mRNA. GIR1 is structurally related to group I ribozymes raising the question about how two closely related ribozymes can carry out very different reactions. Modelling of GIR1 based on new biochemical and mutational data shows an extended substrate domain containing a GoU pair distinct from the nucleophilic residue that dock onto a catalytic core showing a different topology from that of group I ribozymes. The differences include a core J8/7 region that has been reduced and is complemented by residues from the pre-lariat fold. These findings provide the basis for an evolutionary mechanism that accounts for the change from group I splicing ribozyme to the branching GIR1 architecture. Such an evolutionary mechanism can be applied to other large RNAs such as the ribonuclease P.