Skip to main content

Trans Hammerhead Ribozyme: Ligation vs. Cleavage

  • Chapter
  • 1053 Accesses

Abstract

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.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Amarzguioui, M. and Prydz, H. (1998) Hammerhead ribozyme design and application. Cell. Mol. Life Sci. 54, 1175–1202.

    Article  PubMed  CAS  Google Scholar 

  • Blount, K.F. and Uhlenbeck, O.C. (2002) Internal equilibrium of the hammerhead ribozyme is altered by the length of certain covalent cross-links. Biochemistry 41, 6834–6841.

    Article  PubMed  CAS  Google Scholar 

  • Burke, D.H. and Greathouse, S.T. (2005). Low-magnesium, trans-cleavage activity by type III, tertiary stabilized hammerhead ribozymes with stem I discontinuities. BMC Biochemistry 6, 14.

    Article  PubMed  Google Scholar 

  • 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.

    CAS  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 

  • Chetverina, H.V., Demidenko, A.A., Ugarov, V.I. and Chetverin, A.B. (1999) Spontaneous rearrangements in RNA sequences. FEBS Lett. 450, 89–94.

    Article  PubMed  CAS  Google Scholar 

  • Citti, L. and Rainaldi, G. (2005) Synthetic hammerhead ribozymes as therapeutic tools to control disease genes. Curr. Gene Ther. 5, 11–24.

    PubMed  CAS  Google Scholar 

  • Conaty, J., Hendry, P. and Lockett, T.J. (1999) Selected classes of minimised hammerhead ribozymes have very high cleavage rates at low Mg2+ concentration. Nucleic Acids Res. 27, 2400–2407.

    Article  PubMed  CAS  Google Scholar 

  • Fedor, M.J. and Uhlenbeck, O.C. (1992) Kinetics of intermolecular cleavage by hammerhead ribozymes. Biochemistry 31, 12042–12054.

    Article  PubMed  CAS  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.

    CAS  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.

    CAS  Google Scholar 

  • Hendry, P. and McCall, M. (1996) Unexpected anisotropy in substrate cleavage rates by asymmetric hammerhead ribozymes. Nucleic Acids Res. 24, 2679–2684.

    Article  PubMed  CAS  Google Scholar 

  • Hertel, K.J. and Uhlenbeck, O.C. (1995) The internal equilibrium of the hammerhead ribozyme reaction. Biochemistry 34, 1744–1749.

    Article  PubMed  CAS  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 

  • Joyce, G.F. (2002) The antiquity of RNA-based evolution. Nature 418, 214–221.

    Article  PubMed  CAS  Google Scholar 

  • Kuznetsova, M., Fokina, A., Lukin, M., Repkova, M., Venyaminova, A. and Vlassov, V. (2003) Catalytic DNA and RNA for targeting MDR1 mRNA. Nucleosides Nucleotides Nucleic Acids 23, 1521–1523.

    Article  Google Scholar 

  • Kuznetsova, M., Novopashina, D., Repkova, M., Venyaminova, A. and Vlassov, V. (2004) Binary hammerhead ribozymes with high cleavage activity. Nucleosides Nucleotides Nucleic Acids 24, 1037–1043.

    Article  Google Scholar 

  • Muller, U.F. (2006) Re-creating an RNA world. Cell. Mol. Life Sci. 63, 1278–1293.

    Article  PubMed  CAS  Google Scholar 

  • Nelson, J.A., Shepotinovskaya, I. and Uhlenbeck, O.C. (2005) Hammerheads derived from sTRSV show enhanced cleavage and ligation rate constants. Biochemistry 44, 14577-14585.

    Article  PubMed  CAS  Google Scholar 

  • Penedo, J.C., Wilson, T.J., Jayasena, S.D., Khvorova, A. and Lilley, D.M. (2004) Folding of the natural hammerhead ribozyme is enhanced by interaction of auxiliary elements. RNA. 10, 880–888.

    Article  PubMed  CAS  Google Scholar 

  • Peracchi, A. (2004) Prospects for antiviral ribozymes and deoxyribozymes. Rev. Med. Virol. 14, 47–64.

    Article  PubMed  CAS  Google Scholar 

  • Przybilski, R. and Hammann, C. (2006) The hammerhead ribozyme structure brought in line. ChemBioChem 7, 1641–1644.

    Article  PubMed  CAS  Google Scholar 

  • Ruffner, D.E., Stormo, G.D. and Uhlenbeck, O.C. (1990) Sequence requirements of the hammerhead RNA self-cleavage reaction. Biochemistry 29, 10695–10702.

    Article  PubMed  CAS  Google Scholar 

  • Salehi-Ashtiani, K. and Szostak, J.W. (2001) In vitro evolution suggests multiple origins for the hammerhead ribozyme. Nature 414, 82–84.

    Article  PubMed  CAS  Google Scholar 

  • Schubert, S. and Kurreck, J. (2004) Ribozyme- and deoxyribozyme-strategies for medical applications. Curr. Drug Targets 5, 667–681.

    Article  PubMed  CAS  Google Scholar 

  • Simorre, J.P., Legault, P., Hangar, A.B., Michiels, P. and Pardi, A. (1997) A conformational change in the catalytic core of the hammerhead ribozyme upon cleavage of an RNA substrate. Biochemistry 36, 518–525.

    Article  PubMed  CAS  Google Scholar 

  • Spirin, A.S. (2002) Omnipotent RNA. FEBS Lett. 530, 4–8.

    Google Scholar 

  • Stage-Zimmermann, T.K. and Uhlenbeck, O.C. (1998) Hammerhead ribozymes kinetics. RNA 4, 875–889.

    Article  PubMed  CAS  Google Scholar 

  • Stage-Zimmermann, T.K. and Uhlenbeck, O.C. (2001) A covalent crosslink converts the hammerhead ribozyme from a ribonuclease to an RNA ligase. Nat. Struct. Biol. 8, 863–867.

    Article  PubMed  CAS  Google Scholar 

  • Szatmary, E. (1999) The origin of the genetic code. Amino acids as cofactors in an RNA world. Trends Genet. 15, 223–229.

    Article  Google Scholar 

  • Tanner, N.K. (1999) Ribozymes: the characteristics and properties of catalytic RNAs. FEMS Microbiol Rev. 23, 257–275.

    Article  PubMed  CAS  Google Scholar 

  • Vorobjeva, M., Gusseva, E., Repkova, M., Kovalev, N., Zenkova, M., Venyaminova, A. and Vlassov, V. (2005a) Modified binary hammerhead ribozymes with high catalytic activity. Nucleosides Nucleotides Nucleic Acids 25, 1105–1109.

    Article  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 

  • Vorobjeva, M., Zenkova, M., Venyaminova, A. and Vlassov, V. (2006) Binary hammerhead ribozymes with improved catalytic activity. Oligonucleotides 16, 239–252.

    Article  PubMed  CAS  Google Scholar 

  • Weinberg, M.S. and Rossi, J.J. (2005) Comparative single-turnover kinetic analyses of trans-cleaving hammerhead ribozymes with naturally derived non-conserved sequence motifs. FEBS Lett. 579, 1619–1624.

    Article  PubMed  CAS  Google Scholar 

  • Westholf, E. (2007) A tale in molecular recognition: the hammerhead ribozyme. J. Mol. Recogn. 20, 1–3.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Vorobjeva, M., Privalova, A., Venyaminova, A., Vlassov, V. (2008). Trans Hammerhead Ribozyme: Ligation vs. Cleavage. In: Dobretsov, N., Kolchanov, N., Rozanov, A., Zavarzin, G. (eds) Biosphere Origin and Evolution. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-68656-1_10

Download citation

Publish with us

Policies and ethics