Ribozymes are the RNA molecules that like enzymes (protein) are capable of catalyzing a biological reaction and are also called molecular scissors. Ribozymes catalyze a particular reaction either by the hydrolysis of one of their own phosphodiester bonds or by hydrolysis of bonds in other RNA. Discovery of the catalytic role of RNA suggest that may be it was RNA, not protein that have played the key role in evolution. Ribozymes act on RNA molecules and cut it into smaller fragments and like all other enzymes; they can be recovered after the reaction as such. Ribozymes were first discovered by Cech in 1987. Sidney altman and Thomas R.Cech was awarded by Nobel Prize in 1989 for the discovery of ribozymes. Ribozymes are found naturally inside many organisms. Common natural ribozymes include peptidyl transferase 23s rRNA, RNase P, group I & group II introns, hammerhead ribozymes, hairpin ribozymes, leadzyme (initially synthesized artificially but now its natural occurrence has been proved). Ribozymes joins up with the RNA and cuts it into small pieces. Thus the corresponding protein is not produced.
Depending upon the site of action, ribozymes are of two types:-
1) Cis-acting ribozymes
Cis-acting ribozymes are those, where catalytic side main and cleavage site lies on the same strand. Examples include group I introns, hepatitis delta virus (HDV) and Neurospora VS RNA.
2) Trans- acting ribozymes
Trans acting ribozymes are the ribozymes where catalytic domain comprises of one strand and the cleavage site lies on the external RNA or DNA substrate. Thus the ribozymes and its target comprises of two different strands. Examples include RNase P, hammerhead ribozymes, and hairpin ribozymes.
A laboratory in Strasbourg is currently making the use of ribozymes for the study of involvement of certain genes in the onset of spinal muscular atrophy. This disease causes the degeneration of both muscle and nerve cells of the affected person.
Examples of ribozymes
Ribonuclease P is the only naturally occurring trans-acting ribozyme. It acts on tRNA and can selectively cut more than 60 tRNA precursors to produce mature tRNA. These mature tRNAs are now capable of carrying amino acids from cytoplasm to ribosomes for translation. This enzyme is composed of protein and RNA (ribonucleoprotein). Protein part of this enzyme increases the efficiency of the ribozymal part.
Group I & II introns
Introns are the sequences in the gene which do not produce proteins i.e. non coding sequences. These have the capability to act like ribozymes. It was well known now that group I and group II introns can act on and catalyze the cleavage of its own i.e. they are cis acting. Their presence in pre-mRNA causes the splicing of introns that result in mature mRNA.
These are small, catalytic RNA which have the capability to act on its own strand and cut into two parts. Hammerhead ribozymes have a common basic structure, which involved 3 stem loops with a highly conversed residue. This conserved residue is most important, as it has the catalytic power. Mechanism of cleavage involves the attack of 2' hydroxyl oxygen of a catalytic site cytosine on the phosphorus atom attached to the 3' carbon of same conserved residue. This cause breakdown of sugar phosphate backbone and produce 2', 3' cyclic phosphate.
Applications of ribozymes
Ribozymes are used to develop new drugs and protocols for the gene therapy.
HIV & AIDS: - ribozymes can be designed which can specifically cleave the mRNA and interfere with different stages of viral life cycle. Ribozymes can be designed and expressed to interfere with the viral packaging of HIV. For hammerhead and hairpin ribozymes, there are hundreds of potential sites along the HIV genome.
In conclusion, of all these above facts conclude that RNA besides carrying the genetic information can also act as enzyme and catalyzes the biological reaction. That, it is the RNA molecule and not the protein that also played a key role in the evolution.
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