Ribozomes Are Ribonucleic Acid That Act As Catalysts Biology Essay

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Ribozomes are ribonucleic acid (RNA) molecules that function similarly to enzymes in that they act as catalysts. They can either catalyse their own hydrolysis of phosphodiester bonds or different RNAs. The first ribozymes were discovered in the 1980s by Thomas R. Cech and were only thought to function as enzymes, but however Jack W. Szostak and Charles Wilson believed that they manufactured ribozymes capable of catalytic functions (Szostak & Wilson, 1995). Ribozymes can be split in to two groups, which are the cis acting ribozymes in which the main cleaving site lies internally on the same RNA strand and trans in which the main cleaving site is on the external strand. Ribozymes can either catalyse own hydrolysis of phosphodiester bonds or different RNAs. They are known as 'molecular scissors' because they can cut the RNA in a gene, to turn off the gene and once this happens, the effect at the molecular level of turning it off can be studied. However since there are large number of RNA's in different genes, you have to take consideration that cutting one piece of RNA could turn off many other genes than the ones intended, so therefore it was to be carefully judged and analysed.

Naturally occurring ribozymes are classified into numerous categories due to their specific three dimensional structures and characteristics. They are; the hammerhead ribozyme, tetrahymena group I and II intron, hairpin ribozyme, RNase P and hepatitis delta virus ribozyme. The hammerhead ribozyme which was named so because of the observed resemblance of a hammerhead in its secondary structure, along with the Neurospora Varkud satellite and the hairpin ribozyme, which are naturally occurring small self-cleaving RNA critical for viral replication and are also active in vivo without the presence of any protein factors. They are all small RNA nucleotides that perform site-specific self-cleavage (Sharmeen, et al., 1988). However the RNase P and the group I and II introns are much larger and contain several hundred nucleotides and are more structurally complex than the smaller ones (Kruger K, et al., 1982).These ribozymes are extremely highly folded and this gives it their main structure and also enables them to attach to different sites very specifically or even on their own sites. These folds along with the twists in the RNA will enable the robozyme to catalyse the reactions.

The first ribozyme to be discussed is the hammerhead ribosyme, which contains an extremely preserved core of residue for cleavage and three base paired stems. The reaction involving the cleavage starts by the attacking of the 2-hydroxyl oxygen on the cytosine catalytic site on an atom of phosphorus bonded to the 3-carbon of the same residue. This attack on the 2-hydroxyl oxygen breaks the backbone phosphate sugar and makes a 2', 3-cyclic phosphate. The ionized form of 2-hydroxyyl oxygen is stabilized by a bound metal to the active site of the ribonucleases, which advances the catalytic attack. The wishbone-shaped structure of the hammerhead ribozyme comes about when the DNA substitute's part of the RNA and this inhibits the catalyst because there are no 2-hydroxyl groups in DNA (Pley, et al., 1994).

The second ribozyme to be discussed is the ribonuclease (RNase). This is a common enzyme found in this day and age that catalyses the splitting of the RNA into smaller compounds. A type of this is the RNase P, which acts in the same way as a protein because it behaves as a catalyst. The RNase P in bacteria contains 2 components; one of which is an RNA chain (M1 RNA) and the other is the polypeptide chain (C5 protein). These components are both required for the functioning in vivo, but however when it comes to in vitro, the M1 RNA can functions on its own as a catalyst. The RNase P main function is to cleave off the extra sequences of RNA on the tRNA molecules.

The third and final ribozyme to be discussed is the hairpin ribozyme, which is a type of ribozyme that catalyses its own cleavage and it is found in the RNA satellites of plan viruses like the hammerhead ribozyme. The minimum hairpin substrate complex, when folded into a secondary structure consists of two domains that contain short base paired helices, which are separated by a loop. The first domain contains loop A with helix 1 and 2, the second domain contains loop B with helix 3 and 4. The two domains contain a covalent bond through a phosphodiester linkage that connects the second helix to the third, and they must interact with each other to carry out catalysis. The name hairpin ribozyme was named so because, when there's the condition of low ionic strength the two domains to go on top of each other and this will then create the inactive structure which bears a resemblance to a hairpin.

The 3D image of the structure of the hairpin ribozyme (Salter, J et al., (2006)).

The 3D image of the structure of hepatitis delta virus ribozyme (Ferré-D'Amaré AR, Zhou K, Doudna JA (1998)).

http://upload.wikimedia.org/wikipedia/commons/thumb/8/8d/PDB_1cx0_EBI.jpg/200px-PDB_1cx0_EBI.jpg http://upload.wikimedia.org/wikipedia/commons/thumb/4/45/Hairpin-ribozyme-crystal-structure-UR0109.jpg/300px-Hairpin-ribozyme-crystal-structure-UR0109.jpg

There are also artificial as well as naturally occurring ribosymes. The artificially modified ribozymes are enormously important because they can be used as therapeutic agents, biosensors or gene discovery. Therefore ever since naturally occurring ribozymes were discovered, there has been vast work done developing artificial ribozymes. These ribozymes properties make them useful for genomic research and discoveries, so therefore they can be prepared and modified to target specific gene transcripts. Furthermore another major use for ribozymes is when there used as therapeutic agents and the development of new drugs. There has been immense number of work done in the past and still being carried out on using vectors that express ribozymes to cleave on the crucial gene products and also the therapeutic effects it has on many diseases (Sarva, 1990). Ribozymes can be used in human clinical trial on HIV to protect the cells against viral effects and by doing this promote survival of other cells, which in time will lead increased therapeutic effects. The ribozyme therapy could also be used in targeting early viral replication by inhibiting the replication of the RNA in the viral genes.

Finally therefore looking at all the above facts it is clear that RNA are important can show characteristics of an enzyme to catalyse reaction as well as carrying genetic information for the body. All these ribozymes can be designed in the future to prevent disease and infections and therefore there essential to any research done in preventing disease. In the future artificial ribozymes could be specifically made that will act as a switch in the body, which will be turned on in the presence of infections by stopping the viral entry to the body or by specifically cleaving the viral RNA, which should halt viral replication. This method should be more developed and researched because I believe RNA are the main building blocks of life and existed before Deoxyribonucleic acid (DNA).

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