For Biophysics Week, members of the Early Careers Committee have written short summaries of classical biophysics studies, accessible to scientists and non-scientists alike.

This lay summary about ribozymes was written by Trusher Patel, University of Lethbridge.

 

Ribozymes

Biomolecules such as proteins, nucleic acids (RNA/DNA), lipids and carbohydrates play a variety of important roles in biological processes. One such role is catalytic activities performed by enzymes. Traditionally, such enzymes were considered as proteins in nature. In 1982, Kruger et al demonstrated ‘self-splicing RNA’ that could cleave and catalyze phosphodiester bonds, without requiring any additional factors (Kruger et al. 1992). This finding was a major breakthrough that would eventually lead to Nobel Prize in Chemistry for Drs. Thomas Cech and Sidney Altman in 1989. Dr. Altman’s group in 1983 demonstrated that the RNA subunits of E. coli ribonuclease P purified can cleave tRNA precursor molecules, an essential step in tRNA maturation (Guerrier-Takada et al. 1983). Subsequently, the hammerhead ribozyme, the smallest one known so far, was identified from plant viruses and viroids (Prody et al. 1986 and Hutchins et al. 1986). The identification of ribozymes led to a fascinating ‘RNA World’ hypothesis suggesting that RNA acted as genetic material and as a catalyst, long before the formation of DNA and proteins, in self-replicating organisms (Gilbert 1986). Subsequent identification of other ribozymes, including the one from the hepatitis delta virus (Been and Wickham), strengthen the RNA world hypothesis. However, over the years, the hypothesis has also been challenged. The ribozymes have been explored to treat viral infections; however, their clinical applications are yet to be realized.

 

Reference:

Kruger, K.; Grabowski, P.J.; Zaug, A.J.; Sands, J.; Gottschling, D.E.; Cech, T.R. Self-splicing RNA: Autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 1982, 147

Guerrier-Takada, C.; Gardiner, K.; Marsh, T.; Pace, N.; Altman, S. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 1983, 849

Prody, G.A.; Bakos, J.T.; Buzayan, J.M.; Schneider, I.R.; Bruening, G. Autolytic processing of dimeric plant virus satellite RNA. Science 1986, 1577

Hutchins, C.J.; Rathjen, P.D.; Forster, A.C.; Symons, R.H. Self-cleavage of plus and minus RNA transcripts of avocado sunblotch viroid. Nucleic Acids Res. 1986, 3627

Gilbert, W. Origin of life: The RNA world. Nature, 1986, 319, 618

Been, M. D. & Wickham, G. S. Self-cleaving ribozymes of hepatitis delta virus RNA. Eur. J. Biochem. 1997, 247, 741.

 

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