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FOCUS ON RNA
THE CATALYTIC DIVERSITY OF RNAS
Martha J. Fedor* and James R. Williamson*
Abstract | The natural RNA enzymes catalyse phosphate-group transfer and peptide-bond formation. Initially, metal ions were proposed to supply the chemical versatility that nucleotides lack. In the ensuing decades, structural and mechanistic studies have substantially altered this initial viewpoint. Whereas self-splicing ribozymes clearly rely on essential metal-ion cofactors, self-cleaving ribozymes seem to use nucleotide bases for their catalytic chemistry. Despite the overall differences in chemical features, both RNA and protein enzymes use similar catalytic strategies.
RIBOZYME
An enzyme in which RNA functions as the catalytic component.
GROUPI SELF SPLICING INTRONS
A group of catalytic RNAsthat carry out phosphodiester-cleavage and -ligation reactions, which result in the removal of noncoding intronic sequences and splicing of coding exon sequences. Group-I introns were the first class of catalytic RNAs to be discovered.
S 2TYPE INLINE MECHANISM
The chemical term for a class of nucleophilic substitution reactions that involve a concerted attack of a nucleophile and the departure of a leaving group.
Catalytic RNAs or RIBOZYMES provide a window into a primordial RNA world from which modern biology might have evolved1. Contemporary roles for RNA catalysis in the modern protein world can still be found in the regulation of gene expression and in protein synthesis25. Several recent high-resolution structures of self-cleaving and self-splicing RNAs have provided close-up views of the active sites of the hammerhead612, hepatitis delta virus (HDV)13,14 and hairpin15,16 self-cleaving RNAs and GROUPI SELFSPLICING INTRONS1720. The structure of the ribosome3 has given us a picture of the peptidyl-transferase centre, which is the ribosome active site21,22. Numerous mechanistic studies that have been carried out over more than 20 years since ribozymes were first discovered can now be compared and contrasted with the corresponding structures, providing new insights into how RNA enzymes use their functional groups for catalysis.
Naturally occurring ribozymes catalyse phosphate-group transfer through two types of chemical reaction that differ in their reaction products BOX 1. The small
self-cleaving RNAs catalyse reversible phosphodiester-cleavage reactions that generate 5-hydroxyl and 23-cyclic-phosphate termini. Ribonuclease (RNase) P the ubiquitous ribozyme that is responsible for cleaving 5-flanking sequences from precursor tRNAs and self-splicing introns catalyse phosphodiester-cleavage and -ligation reactions that produce 5-phosphate and 3-hydroxyl termini. Both kinds of...