Comparative Enzymology and Structural Biology of RNA Self-Cleavage

Self-cleaving hammerhead, hairpin, hepatitis delta virus, and glmS ribozymes comprise a family of small catalytic RNA motifs that catalyze the same reversible phosphodiester cleavage reaction, but each motif adopts a unique structure and displays a unique array of biochemical properties. Recent structural, biochemical, and biophysical studies of these self-cleaving RNAs have begun to reveal how active site nucleotides exploit general acid-base catalysis, electrostatic stabilization, substrate destabilization, and positioning and orientation to reduce die free energy barrier to catalysis. Insights into the variety of catalytic strategies available to these model RNA enzymes are likely to have important implications for understanding more complex RNA-catalyzed reactions fundamental to RNA processing and protein synthesis.