RNA folding and catalysis

Author: Lilley D.M.J.1

Source: Genetica, Volume 106, Number 1-2, October 1999 , pp. 95-102(8)

Publisher: Springer

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Abstract:

Catalysis in RNA is intimately connected to the folding. The small nucleolytic ribozymes function by a nucleophilic attack of the 2prime-oxygen on the 3prime-phosphate, in an S_N2 mechanism. This requires an alignment of the 2prime-O, 3prime-P and 5prime-O, that does not occur in normal A-form RNA. It is therefore likely that structural distortion plays a major role in the enhancement of the reaction rate, facilitating the trajectory into the in-line transition state. Given the polyelectrolyte nature of nucleic acids, metal ions are critical to folding processes in RNA. We have shown that two small nucleolytic ribozymes, the hammerhead and hairpin ribozymes, undergo metal ion-induced folding processes. The hammerhead ribozyme folds in two stages, each of which is induced by the binding of a single structural ion. The first corresponds to the formation of the ribozyme scaffold, while the second is the formation of the catalytic core of the ribozyme. By contrast, the hairpin ribozyme undergoes a single folding event induced by the binding of at least two metal ions, and involves the close interaction between two internal loops to form the active ribozyme.

Keywords: ribozymes; metal ions; hammerhead; hairpin; transesterification reaction

Language: English

Document Type: Regular paper

Affiliations: 1: CRC Nucleic Acid Structure Research Group, Department of Biochemistry, University of Dundee, Dundee DD1 4HN, UK

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