Ferré-D'Amaré Lab Research > Catalytic RNAs
Catalytic RNAs (also called ribozymes) are responsible for essential physiologic functions in all organisms. An atomic-level understanding of their mechanism of action that is grounded in the principles of physics and chemistry is a prerequisite for the manipulation of ribozyme function in health and disease. By determining their crystal structures in multiple functional states, we have generated 'molecular movies' of the hairpin and glmS ribozymes in action. These studies revealed how ribozymes can preferentially stabilize the transition state of their reactions, and how the glmS ribozyme can employ a small molecule as a coenzyme. We have also analyzed several artificial ribozymes with biotechnological applications, including an RNA ligase ribozyme and flexizyme, an aminoacil-tRNA synthetase.
• Lau, M.W.L & Ferré-D'Amaré, A.R. An in vitro evolved glmS ribozyme has the wild-type fold but loses coenzyme dependence. Nature Chemical Biology 9, 805-810 (2013). [abstract]
• Ferré-D'Amaré, A.R. & Scott, W.G. The small self-cleaving ribozymes. Cold Spring Harbor Persp. Biol. (published online September 15, 2010). [abstract]
• Xiao, H., Murakami, H., Suga, H. & Ferré-D'Amaré, A.R. Structural basis of specific tRNA aminoacylation by a small in vitro selected ribozyme. Nature 454, 358-361 (2008). [abstract]
• Klein, D.J., & Ferré-D’Amaré, A.R. Structural basis of glmS ribozyme activation by glucosamine-6-phosphate. Science 313, 1752-1756 (2006). [abstract]
• Rupert, P.B., Massey, A., Sigurdsson, S.Th. & Ferré-D'Amaré, A.R. Transition state stabilization by a catalytic RNA. Science 298, 1421-1424 (2002). [abstract]