Ribozymes

The discovery in 1982 that an intron of the protozoan Tetrahymena can excise itself from precursor ribosomal RNA in the absence of protein challenged the belief that only proteins can act as biological catalysts. The new field of RNA enzymology emerged to study such phenomena, and catalytic RNAs have now been shown to fold up to form complex three-dimensional surfaces that can bind specific substrates and break and join RNA chains. Today, the catalytic mechanisms of one or two RNA enzymes (or ribozymes) are understood as well as the mechanisms of action of typical protein enzymes. Several crystallographic structures are now available for one small catalytic RNA, the hammerhead, and the structure of a subdomain of one large catalytic RNA, the Tetrahymena ribozyme, has also been solved crystallographically. Much has been learned about the pathways by which complex RNA enzymes assemble into their final folded structures. In addition, ribozymes targeted against viral RNA genomes and the messenger RNA (mRNA) products of disease-associated genes have found their way into pharmaceutical laboratories, if not into pharmacies.