Article
- The EMBO Journal (2008) 27, 667 - 678
- doi:10.1038/emboj.2008.4
Published online: 24 January 2008
Subject Category:
Molecular modelling of the GIR1 branching ribozyme gives new insight into evolution of structurally related ribozymesEMBO Open
Bertrand Beckert1, Henrik Nielsen2,3, Christer Einvik4, Steinar D Johansen3, Eric Westhof1 and Benoît Masquida1
- Architecture et Réactivité de l'ARN, Université Louis Pasteur de Strasbourg, IBMC, CNRS, Strasbourg, France
- Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
- Department of Molecular Biotechnology, Institute of Medical Biology, University of Tromsø, Tromsø, Norway
- Department of Pediatrics, University Hospital of North Norway, Tromsø, Norway
Correspondence to:
Benoît Masquida, Architecture et Réactivité de l'ARN, Université Louis Pasteur de Strasbourg, IBMC, CNRS, 15 rue René Descartes, Strasbourg 67084, France. Tel.: +333 88 41 70 45; Fax: +333 88 60 22 18; E-mail: b.masquida@ibmc.u-strasbg.fr
Henrik Nielsen, E-mail: Hamra@imbg.ku.dk
Received 10 August 2007; Accepted 4 January 2008
Abstract
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.
Keywords:
- GIR1 branching ribozyme,
- group I intron,
- RNA evolution,
- 3D modelling of RNA
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