Ribozymes

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Ribozymes (ribo nucleic acid enzymes ) are RNA molecules that can catalyse specific reactions in a similar way to protein enzymes. The term ribozyme was first used in 1982 by Altman and Cech in their independent research into catalytic research for which they were jointly awarded the 1989 Nobel Prize in Chemistry [1][2][3]  although it had been postulated earlier that RNA could act as an enzyme due to its propensity to form complex folded structures [4] . The discovery of ribozymes proved that RNA could act as both an information storage molecule and catalytic molecule and so provided strong support for the RNA world hypothesis

Ribozyme is an RNA molecules which possess a catalytic activity due to the tertiary structure that it forms [5]. One of the examples of the ribozyme is the 23S rRNA which is responsible for catalyzing the linkage of to adjacent amino acids by a peptide bond during the process of translation [6]. The ribozymes were first discovered by two American scientist: Thomas Cech and Sidney Altman in 1970s. 20 years later they won a Nobel Prize for "discovery of catalytic properties of RNA" [7]. Some ribozymes can be known to be 'self splicing' as shown in an experiement performed by Thomas Cech in the 1980s. This property was seen to be present in the Tetrahymena ribozyme which is able to form smaller RNA sections from an RNA strand. This conclusion was made as intron removal occured without there being any protein catalyst present. All forms of ribozymes are often used as evidence for the RNA world hypothesis.

The hammerhead ribozyme aids self-cleavage of RNA in some organisms and are being investigated for their ability to treat some forms of cancer as well as HIV infection[8][9][10]

Ribozyme activity

The most significant evidence of ribozymes shown in current-day cells is found in the ribosome where RNA forms a ribonucleoprotein (RNP)[11]. RNA carries out the peptidyl transferase reaction, the key step in polypeptide synthesis, and no protein comes within 18 angstroms of where the peptide bond is formed[12]

Ribozymes also form an integral element of RNA splicing. In eukaryotes, the majority of RNA splicing is driven by the spliceosome, a large and complex RNP consisting of small nuclear ribonucleic particles and protein[13]. The spliceosome binds to pre-messenger RNA (mRNA) and removes introns leaving only exons needed for protein synthesis. The spliceosome is similar to the ribosome in that the presence of RNA suggests it was once a process carried out solely by RNA. Furthermore, RNA was shown to have the ability to self-splice without any protein involvement by introns that form a ribozyme and carry out the function of the spliceosome[14].

References

  1. Guerrier-Takada, C., Gardiner, K., Marsh, T., Pace, N. and Altman, S. (1983) 'The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme', Cell, vol. 35, no. 3, December, pp. 849-857.
  2. Kruger, K., Grabowski, P.J., Zaug, A.J., Sands, J., Gottschling, D.E. and Cech, T.R. (1982) 'Self-splicing RNA: Autoexcision and autocyclization of the ribosomal RNA intervening sequence of tetrahymena', Cell, vol. 31, no. 1, November, pp. 147-157.
  3. "The Nobel Prize in Chemistry 1989". Nobelprize.org. Nobel Media AB 2014. Web. 27 Nov 2014. <http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1989/>
  4. Woese, C.R. (1967) The genetic code: the molecular basis for genetic expression, New York: Harper and Row.
  5. Berg J., Tymoczko J., Stryer L. (2007) Biochemistry, 6th edition, New York: WH Freeman.
  6. Berg J., Tymoczko J., Stryer L. (2007) Biochemistry, 6th edition, New York: WH Freeman.
  7. Nobelprize.org "The Nobel Prize in Chemistry 1989". Available at: http://nobelprize.org/nobel_prizes/chemistry/laureates/1989/ (last accessed 5 Dec 2010)
  8. http://www.callutheran.edu/BioDev/omm/hhribozyme/hhribo.htm
  9. Kleinsmith L., Kish V (1995). Principles of cell and molecular biology. 2nd ed. New York: HarperCollins. 482.
  10. http://www.callutheran.edu/BioDev/omm/hhribozyme/hhribo.htm
  11. Cech, T.R. (2000) 'The Ribosome is a Ribozyme', Science, vol. 289, no. 5481, August, pp. 878-879.
  12. Nissen, P., Hansen, J., Ban, N., Moore, P.B. and Steitz, T.A. (2000) 'The Structural Basis of Ribosome Activity in Peptide Bond Synthesis', Science, vol. 289, no. 5481, August, pp. 920-930.
  13. Will, C.L. and Lührmann, R. (2011) 'Spliceosome Structure and Function', Cold Spring Harbor Perspectives in Biology, vol. 3, no. 7, July, Available: doi: 10.1101/cshperspect.a003707.
  14. Kruger, K., Grabowski, P.J., Zaug, A.J., Sands, J., Gottschling, D.E. and Cech, T.R. (1982) 'Self-splicing RNA: Autoexcision and autocyclization of the ribosomal RNA intervening sequence of tetrahymena', Cell, vol. 31, no. 1, November, pp. 147-157.
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