Ribozymes are catalytic RNA molecules involved in protein synthesis. Most biological catalysts are enzymes and until around four decades ago, experts believed that only enzymes could serve as catalysts in cells.
In 1967, Carl Woese, Francis Crick, and Leslie Orgel proposed that RNA could in fact perform catalytic functions. They based their suggestion on the finding that RNA could form secondary structures. In the 1980s, the research groups of Thomas Cech and Sidney Altman showed that some catalysts are indeed made of RNA.
Thomas Cech and Sidney Altman went on to win the Nobel Prize in chemistry in 1989 for establishing the catalytic properties of RNA and in 1982, Kelly Kruger and colleagues introduced the term ribozyme in a paper published in the journal Cell.
Cech demonstrated that an intron in the rRNA of protozoans that needed to be removed before the rRNA could function, could excise itself from precursor RNA and carry out an autocatalytic reaction to re-fuse the two ends. Altman demonstrated that RNA from an RNA complex called ribonuclease P cleaves a tRNA precursor, which gives rise to mature tRNA.
Many scientists now believe that at some point in evolution, early forms of life relied on RNA for catalyzing chemical reactions and storing genetic information. This period is sometimes referred to as the “RNA World.” According to the RNA World hypothesis, life forms later evolved to rely on proteins and DNA because in comparison, RNA was less stable and had weaker catalytic capabilities.
The strongest evidence to support the RNA World hypothesis is that the ribosome, which is responsible for building proteins, is in fact a ribozyme. Analysis has shown that although the ribosome is composed of protein, a key mechanism in translation is catalyzed by RNA and not a protein. This supports the theory that earlier life forms would have relied on RNA for chemical reactions and the storage of genetic information.
In addition to providing a better understanding of evolution, the discovery that RNA can act as a biocatalyst is likely to provide a useful tool in gene technology, offering the potential to design defence mechanisms against dangerous infections. Specifically designed ribozymes could potentially be used to shear genes and destroy RNA molecules that give rise to harmful effects in certain organisms. By cutting and destroying virus RNA, for example, an organism could gain protection against viral infections. Gene shearing could also be used to cure the human cold or to create plants that are resistant to viruses. A more challenging application would be the use of gene shears to correct genetic disorders. This would probably require the synthesis of new RNA enzymes and an improved understanding of the mechanisms underlying the catalytic ability of RNA.
Further Reading