Introduction to The Catalytic RNA

The idea that only proteins could possess enzymatic activity was deeply rooted in early biochemistry. The rationale behind this thinking was that only proteins, with their complex threedimensional structures and variety of side-chain groups, had the flexibility to create the active sites that catalyze biochemical reactions. However, critical studies of systems involved in RNA processing have shown this view to be an oversimplification.
The first examples of RNA-based catalysis were identified in the bacterial tRNA processing enzyme, ribonuclease P (RNase P), and self-splicing group I introns in RNA from Tetrahymena thermophila. For their pioneering work on RNA catalysts, Sidney Altman and Thomas Cech were awarded the 1989 Nobel Prize in Chemistry.
Since the initial discovery of catalytic RNA, several other types of catalytic reactions mediated by RNA have been identified. Importantly, ribosomes, the RNA–protein complexes that manufacture peptides (see the Translation chapter), have been identified as ribozymes, with RNA acting as the catalytic component and protein acting as a scaffold. Additionally, synthetic RNA ribozymes have been engineered to perform an array of chemical reactions, including polymerization of RNA polynucleotides.
Ribozyme has become a general term used to describe an RNA with catalytic activity, and it is possible to characterize the enzymatic activity in the same way as a more conventional enzyme.
Some RNA catalytic activities are directed against separate substrates (intermolecular), whereas others are intramolecular, which limits the catalytic action to a single cycle. The enzyme RNase P is a ribonucleoprotein that contains a single RNA molecule bound to a protein. RNase P functions intermolecularly and is an example of a ribozyme that catalyzes multiple-turnover reactions. Although originally identified in Escherichia coli, RNase P is now known to be required for the viability of both prokaryotes and eukaryotes. The RNA possesses the ability to catalyze cleavage in a tRNA substrate, with the protein component playing an indirect role, probably to maintain the structure of the catalytic RNA.
The two classes of self-splicing introns, group I and group II, are good examples of ribozymes that function intramolecularly. Both group I and group II introns possess the ability to splice themselves out of their respective pre-mRNAs. Although under normal conditions the self-splicing reaction is intramolecular, and therefore single turnover, group I introns can be engineered to generate RNA molecules that have several other catalytic activities related to the
original activity.
The common theme of the reactions performed by catalytic RNA is that the RNA can perform an intramolecular or intermolecular reaction that involves cleavage or joining of phosphodiester bonds in vitro. It is important to note, however, that reactions catalyzed by RNA are not limited to these two reactions. Although the specificity of the reaction and the basic catalytic activity of an RNAmediated reaction is provided by RNA, proteins associated with the RNA may be needed for the reaction to occur efficiently in vivo.
RNA splicing is not the only means by which changes can be introduced in the informational content of RNA. In the process of RNA editing, changes are introduced at individual bases, or bases are added at particular positions within an mRNA. The insertion of bases (most commonly uridine residues) occurs for several genes in the mitochondria of certain unicellular/oligocellular eukaryotes. Like splicing, RNA editing involves the breakage and reunion of bonds between nucleotides, as well as a template for encoding the information of the new sequence.