Trans Hammerhead Ribozyme: Ligation vs. Cleavage
Trans hammerhead ribozymes are considered from the point of view of the RNA world theory. An attempt was made to reconstruct the ‘ancestors’ of contemporary hammerhead ribozymes with improved ligation activity by altering the sequence of trans hammerhead motifs. RNA ligation activity of trans hammerheads was shown to be affected significantly by minor changes in non-conservative regions. In particular, introduction of heptanucleotide bulge into stem III led to the 10-fold increase of ligation rate constant. At that, RNA cleavage was predominant activity in all cases. It was shown that trans hammerhead ribozyme can assemble from two separate short oligoribonucleotides upon binding to RNA substrate. This binary hammerhead ribozyme possesses a higher RNA-cleaving activity than its full-length analog. It can be assumed that such self-assembling multi-subunit catalytic RNAs could exist at early stages of the prebiotic evolution.
KeywordsCatalytic Cycle Hammerhead Ribozyme Association Rate Constant Ligation Efficiency Ligation Activity
Unable to display preview. Download preview PDF.
- Cech, T.R., Zaug, A.J. and Grabowski, P.J. (1981). In vitro splicing of the ribosomal RNA precursor of Tetrahymena: involvement of a guanosine nucleotide in the excision of the intervening sequence. Cell 27, 487–496.Google Scholar
- Chen, X., Li, N. and Ellington, A.D. (2007) Ribozyme catalysis of metabolism in the RNA world. Chem. Biodivers. 4, 633–655.Google Scholar
- Grassi, G., Dawson, P., Guarneri, G., Kandolf, R. and Grassi, M. (2004) Therapeutic potential of hammerhead ribozymes in the treatment of hyper-proliferative diseases. Curr. Pharm. Biotechnol. 5, 369–386.Google Scholar
- 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 35, 849–857.Google Scholar
- Hertel, K.J., Herschlag, D. and Uhlenbeck, O.C. (1994) A kinetic and thermodynamic framework for the hammerhead ribozyme reaction. Biochemistry 33, 3374–3385.Google Scholar
- Spirin, A.S. (2002) Omnipotent RNA. FEBS Lett. 530, 4–8.Google Scholar
- Vorobjeva, M.A., Gusseva, E.V., Venyaminova, A.G. and Vlassov, V.V. (2005b) Binary catalytic RNA. International Workshop “Biosphere Origin and Evolution”. 74–75. Abstracts.Google Scholar