A Mechanistic Comparison of the Varkud Satellite and Hairpin Ribozymes

The hairpin and Varkud satellite ribozymes are two members of the class of nucleolytic ribozymes that catalyze cleavage and ligation reactions at a specific site. Cleavage occurs by a transesterification reaction whereby the 2'-O attacks the adjacent phosphorus with departure of the 5'4) to leave a 2',3'-cyclic phosphate. The structures of both ribozymes are now known. Although the sequences and structures of these ribozymes are generally unrelated, the topological organization and the arrangement of the active sites are the same for both. Both mechanistic and structural data indicate that the ribozymes employ general acid base catalysis to accelerate the transesterification reactions, using guanine and adenine nucleobases as the general base and acid, respectively, in the cleavage reactions. As a class, the nucleolytic ribozymes all appear to use general acid base catalysis; guanine nucleobases in particular are very common participants.