3.19 : Ribozymes

The term ribozyme is used for RNA that can act as an enzyme. Ribozymes are mainly found in selected viruses, bacteria, plant organelles, and lower eukaryotes. Ribozymes were first discovered in 1982 when Tom Cech’s laboratory observed Group I introns acting as enzymes. This was shortly followed by the discovery of another ribozyme, Ribonulcease P, by Sid Altman’s laboratory. Both Cech and Altman received the Nobel Prize in chemistry in 1989 for their work on ribozymes.

Ribozymes can be categorized into two groups depending upon their size – large and small. Large ribozymes can vary in size from a few hundred to several thousand nucleotides. The type I and II introns and bacterial Ribonuclease P are large ribozymes. Small ribozymes are 30 to 150 nucleotides long. They are found in many pathogenic plant viruses and the hepatitis delta virus (HDV), a human pathogen. Hammerhead, hairpin, HDV and Varkud satellite are common types of small ribozymes. Most large ribozymes need metal ions, especially Mg²⁺, for their activity, but metal ions are not necessary for most of the small ribozymes. The glmS ribozyme, in glmS mRNA, is a unique a-ribozyme as it also acts as a riboswitch when glucosamine 6-phosphate is present at high concentrations.

Most naturally occurring ribozymes catalyze self-cleavage breaking phosphodiester bonds present in their own RNA. Unlike a typical protein enzyme, most ribozymes perform a single-turnover reaction because, after self-cleavage, they are no longer active. However, two ribozymes - Ribonulcease P and the 23S RNA in the 50S ribosomal subunit perform different reactions. Bacterial Ribonuclease P is an RNA-protein complex that has endonuclease activity and requires Mg²⁺ ions. Its RNA component acts on the 5' end of premature tRNA to produce the mature 5' end. The 23S RNA present in the ribosome is different from all other known natural ribozymes as instead of phosphoryl transfer reactions, it carries out peptide-bond formation reactions during translation.

As RNA can act as a carrier of genetic information as well as enzymes, it is hypothesized that an “RNA world” may have existed in the past where RNA played an important role in the development of the early life forms. However, with the evolution of complex life forms, proteins with twenty amino acids might have started acting as enzymes and took over the many reactions carried out by the ribozymes. This theory gets support from the in-vitro developed artificial ribozymes that can carry out a myriad of reactions such as amide bond formation, glycosidic bond formation, carbon-carbon bond formation, and oxidation-reduction reactions.