Nucleic Acid Catalysis: Metals, Nucleobases, and Other Cofactors

The discovery of RNA-catalyzed phosphodiester bond cleavage by Cech and Altman in 1982–1983 shattered the paradigm of protein-dependent biological catalysis and opened up new horizons for RNA biology (reviewed in ref (1)). These discoveries ushered in a new era of high activity in RNA biochemistry and structural biology that, in conjunction with developments in genomics, established groundwork for the ensuing explosion in discoveries of other functional but noncoding RNAs. Since the initial discoveries, several classes of naturally occurring and artificially developed ribozymes have been defined. Ribozyme reactions catalyzed in nature include phosphoryl and aminoacyl transfer reactions (Figure ​(Figure1).1). RNA-catalyzed reactions obtained in vitro extend to carbon–carbon bond formation in the Diels–Alderase ribozyme. In vitro selection has also been employed to discover DNA-based enzymes that catalyze a number of different reactions, including RNA cleavage, as in Figure ​Figure11A. Figure 1 Reactions catalyzed by naturally occurring ribozymes. (A) Intramolecular phosphoryl-transfer reaction catalyzed by the “nucleolytic” ribozymes including the hammerhead, hepatitis delta virus (HDV), hairpin, Neurospora VS, and GlmS RNAs. ...

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