By Sally Robertson, BSc
A ribozyme is a ribonucleic acid (RNA) enzyme that catalyzes a chemical reaction. The ribozyme catalyses specific reactions in a similar way to that of protein enzymes.
Also called catalytic RNA, ribozymes are found in the ribosome where they join amino acids together to form protein chains. Ribozymes also play a role in other vital reactions such as RNA splicing, transfer RNA biosynthesis, and viral replication.
The first ribozyme was discovered in the early 1980s and led to researchers demonstrating that RNA functions both as a genetic material and as a biological catalyst. This contributed to the worldwide hypothesis that RNA may have played a crucial role in the evolution of self-replicating systems. This is referred to as the RNA World Hypothesis and today, many scientists believe that ribozymes are remnants of an ancient world that existed before the evolution of proteins. It is thought that RNAs used to catalyse functions such as cleavage, replication and RNA molecule ligation before proteins evolved and took over these catalytic functions, which they could perform in a more efficient and versatile way.
Ribozymes have been extensively investigated by researchers to try and determine their exact structure and function. Scientists have developed synthetic ribozymes in the laboratory that are able to catalyze their own synthesis under specific conditions. One example is the RNA polymerase ribozyme. Using mutagenesis and selection, scientists have managed to develop and improve variants of the Round-18 polymerase ribozyme from 2001. The best variant so far is called B6.61, which can add up to 20 nucleotides to a primer template over a period of 24 hours. After 24 hours, the hydrolysis of its phosphodiester bonds causes the ribozyme to decompose.
Ribozymes may also play an important role in therapeutic areas, acting as molecules that can tailor specific RNA sequences, serving as biosensors and providing a useful tool in areas such as gene research and functional genomics. For example, strands of circular ribozymes celled viriods have been discovered and these can have a devastating effect on plants. The viriods replicate by making copies of themselves based on their own genome and their catalytic properties enable them to undergo self-cleavage and send fragments off to colonize and harm areas of a plant by proliferating and using the genetic material that the plant itself needs. Researchers have now identified a site in these viriods that enables them to self-cleave. The site is less than 30 nucleotides in length and has three stems that form a central loop which is referred to as a “hammerhead.” This structure cleaves very specific RNA sequences to release viable RNA daughter strands. Now, hammerheads of just 19 nucleotides in length have been synthesized that act as highly specific catalysts. Similar ribozymes are also being made that could be used to break up RNA viruses and RNA that is required for the transcription and translation of DNA that contains mutations.
Such detailed studies of RNAs have led to rules being established regarding how they achieve target recognition and based on those rules, scientists have managed to adjust ribozymes so that they target and cleave new RNA molecule targets that would not usually undergo cleavage by ribozymes. This raises the exciting possibility that artificial ribozymes could be used as a therapeutic agents to target RNA molecules that cause diseases such as HIV. In models of such diseases, ribozymes have been successful at achieving this and a ribozyme that has been shown to target and break up the RNA that makes up the HIV virus has already been approved for testing in patients with HIV. In the future, ribozymes may also be used as therapeutic agents in the correction of genetic disorders. They could be used to eliminate abnormal proteins before they even exist by attacking and breaking up the molecules of RNA that are needed for their translation and transcription.
Last Updated: Sep 17, 2015