Small Self-cleaving Ribozymes

The hammerhead, hairpin, hepatitis delta virus (HDV), Varkud Satellite (VS), and glmS ribozymes catalyze sequence-specific intramolecular cleavage of RNA. They range between 50 and 150 nucleotides in length, and are known as the "small self-cleaving ribozymes." Except for the glmS ribozyme that functions as a riboswitch in Gram-positive bacteria, they were originally discovered as domains of satellite RNAs. However, recent studies show that several of them are broadly distributed in genomes of organisms from many phyla. Each of these ribozymes has a unique overall architecture and active site organization. Crystal structures have revealed how RNA active sites can bind preferentially to the transition state of a reaction, whereas mechanistic studies have shown that nucleobases can efficiently perform general acid-base and electrostatic catalysis. This versatility explains the abundance of ribozymes in contemporary organisms and also supports a role for catalytic RNAs early in evolution. Outline 1 Introduction 2 The internal transesterification reaction and its catalysis 3 Overall structures of self-cleaving ribozymes 4 Active site structures and catalytic mechanisms 5 The hairpin ribozyme: Analogy to RNase A 6 The hammerhead ribozyme: Variation on a theme 7 The glmS ribozyme: Co-opting a cofactor 8 The HDV ribozyme: Nucleobase and metal-ion catalysis 9 How widespread are the self-cleaving ribozymes?