1 Section II. Building 18.2, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 RNA and Gene Medicine Program, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 Architecture et Réactivité de l'ARN, Unité Propre de Recherche 9002, Institut de Biologie Moléculaire et Cellulaire, Université de Strasbourg, Centre National de la Recherche Scientifique, 67084 Strasbourg, France;4 Swiss Light Source at Paul Scherrer Institute, 5232 Villigen, Switzerland;5 Synchrotron Soleil, 91190 Saint-Aubin, France;Institut National de la Recherche Agronomique, Unité Biopolymères, Interactions, Assemblages, 44316 Nantes, France; and.6 Department of Medical Biology, University of Tromsø, N-9019 Tromsø, Norway.7 Section II. Building 18.2, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
The lariat-capping (LC) ribozyme is a natural ribozyme isolated from eukaryotic microorganisms. Despite apparent structural similarity to group I introns, the LC ribozyme catalyzes cleavage by a 2',5' branching reaction, leaving the 3' product with a 3-nt lariat cap that functionally substitutes for a conventional mRNA cap in the downstream pre-mRNA encoding a homing endonuclease. We describe the crystal structures of the precleavage and postcleavage LC ribozymes, which suggest that structural features inherited from group I ribozymes have undergone speciation due to profound changes in molecular selection pressure, ultimately giving rise to an original branching ribozyme family. The structures elucidate the role of key elements that regulate the activity of the LC ribozyme by conformational switching and suggest a mechanism by which the signal for branching is transmitted to the catalytic core. The structures also show how conserved interactions twist residues, forming the lariat to join chemical groups involved in branching.
Proceedings of the National Academy of Sciences of the United States of America, 2014, Vol 111, Issue 21, p. 7659-64