Ribozymes (RNA Splicing, DNA Cleavage and RNA Amplification)
Till very recently, enzymatic catalysis was thought to be the exclusive domain of proteins. As shown above in this section, only in recent years it was shown that RNA molecules can cut, splice and assemble themselves without any outside help, thus extending the range of chemistry of enzymes. These RNA molecules working as enzymes, were called ribozymes. It has also been shown that enzymes can also be synthesized chemically, and are then described as chemzymes. For the work on RNA molecules working as ribozymes, two scientists (Thomas R. Cech of- University of Colorado, Boulder and Sidney Altaian of Yale University) were awarded Nobel Prize in 1989. This discovery of RNA molecules working as enzymes has also changed our thinking about origin of life. It is now believed that four billion years ago Earth was an 'RNA world' in which RNA molecules carried out all the processes of life without the help of either protein or DNA.
The discovery of ribozymes can be traced back to 1982, when Thomas Cech, was trying to understand how 'sequences' (including sequences derived from introns) are spliced out of RNA molecules during processing of hnRNA into mRNA, or precursor rRNA into rRNA in Tetrahymena. The discovery was made when it was found that removal of proteinaceous enzymes one by one from a cell free system did not alter the splicing ability of pre-ribosomal RNA. However, these RNA molecules acted only on themselves, not on other molecules. Later in 1983 and 1984, Sidney Altman, using ribonuclease P1 (it consists of RNA + protein and is E. coli RNA processing endonuclease for splicing of tRNA), demonstrated that catalytic activity of ribonuclease P1 resided only in RNA subunit, and protein only helped RNA to perform the enzymatic function. Self cleavage of viroid RNAs or virusoids (satellite RNAs) and catalytic activity of RNAase are other examples of ribozymes. Subsequently it was shown that ribozymes may also bring about (i) cleavage of DNA molecules, and (ii) selective amplification of RNA molecules.