Journal of Molecular Evolution

, Volume 56, Issue 6, pp 711–717 | Cite as

Perfectly Complementary Nucleic Acid Enzymes

Article

Abstract

The ability to maximize the use of available nucleic acid sequence space would have been crucial during the presumed RNA world and confers selective advantage in many contemporary organisms. One way to access sequence space at a higher density would be to make use of both strands of a duplex nucleic acid for the production of functional molecules. As a demonstration of this possibility, two pairs of nucleic acid enzymes were engineered to be perfect complements, each with the capacity to adopt a distinct structure and catalyze a particular chemical transformation. Both members of each pair of enzymes exhibited nearly the same level of activity as the canonical form of the corresponding catalytic motif. The ability to generate functional nucleic acids encoded by both strands of a duplex has implications for the evolution of catalytic nucleic acids and the prospects for realizing maximum functionality from a given genetic sequence.

Keywords

DNAzyme In vitro evolution Nucleic acid catalysis Ribozyme RNA structure RNA world 

References

  1. 1.
    Adelman, JP, Bond, CT, Douglass, J, Herbert, E 1987Two mammalian genes transcribed from opposite strands of the same DNA locus.Science23515141517Google Scholar
  2. 2.
    Buzayan, JM, Gerlach, WL, Bruening, G 1986Non-enzymatic cleavage and ligation of RNAs complementary to a plant virus satellite RNA.Nature323349353Google Scholar
  3. 3.
    Comeron, JM 2001What controls the length of noncoding DNA?Curr Opin Genet Dev11652659PubMedGoogle Scholar
  4. 4.
    Compton, J 1991Nucleic acid sequence-based amplification.Nature3509192PubMedGoogle Scholar
  5. 5.
    Doolittle, WF 1978Genes in pieces: Were they ever together?Nature272581582Google Scholar
  6. 6.
    Fedor, M 2000Structure and function of the hairpin ribozyme.J Mol Biol297269291PubMedGoogle Scholar
  7. 7.
    Forster, AC, Symons, RH 1987Self-cleavage of virusoid RNA is performed by the proposed 55-nucleotide active site.Cell50916PubMedGoogle Scholar
  8. 8.
    Gesteland, RFCech, TRAtkins, JF eds. 1999The RNA world, 2nd ed.Cold Spring Harbor Laboratory PressNew YorkGoogle Scholar
  9. 9.
    Guatelli, JC, Whitfield, KM, Kwoh, DY, Barringer, KJ, Richman, DD, Gingeras, TR 1990Isothermal in vitro amplification of nucleic acids by a multienzyme reaction modeled after retroviral replication.Proc Natl Acad Sci USA8777977802PubMedGoogle Scholar
  10. 10.
    Hampel, A, Tritz, R, Hicks, M, Cruz, P 1990‘Hairpin’ catalytic RNA model: Evidence for helices and sequence requirement for substrate RNA.Nucleic Acids Res18299304PubMedGoogle Scholar
  11. 11.
    Henikoff, S, Keene, MA, Fechtel, K, Fristrom, JW 1986Gene within a gene: Nested Drosophila genes encode unrelated proteins on opposite DNA strands.Cell443342PubMedGoogle Scholar
  12. 12.
    Hill CS (1996) Gen-Probe transcription-mediated amplification: System principles. Gen-Probe Incorporated Technical Document; available at http://www.gen-probe.com/pdfs/tma_whiteppr.pdf
  13. 13.
    Mira, A, Ochman, H, Moran, NA 2001Deletional bias and the evolution of bacterial genomes.Trends Genet17589596PubMedGoogle Scholar
  14. 14.
    Misener, SR, Walker, VK 2000Extraordinarily high density of unrelated genes showing overlapping and intraintronic transcription units.Biochim Biophys Acta1492269270PubMedGoogle Scholar
  15. 15.
    Normark, S, Bergstrom, S, Edlund, T, Grundstrom, T, Jaurin, B, Lindberg, FP, Olsson, O 1983Overlapping genes.Annu Rev Genet17499525Google Scholar
  16. 16.
    Okazaki, Y,  et al. 2002Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.Nature420563573The FANTOM Consortium and the RIKEN Genome Exploratory Research Group Phase I and II TeamCrossRefPubMedGoogle Scholar
  17. 17.
    Ordoukhanian, P, Joyce, GF 1999A molecular description of the evolution of resistance.Chem Biol6881889PubMedGoogle Scholar
  18. 18.
    Prody, GA, Bakos, JT, Buzayan, JM, Schneider, IR, Bruening, G 1986Autolytic processing of dimeric plant virus satellite RNA.Science23115771580Google Scholar
  19. 19.
    Santoro, SW, Joyce, GF 1997A general purpose RNA-cleaving DNA enzyme.Proc Natl Acad Sci USA9442624266PubMedGoogle Scholar
  20. 20.
    Santoro, SW, Joyce, GF 1998Mechanism and utility of an RNA-cleaving DNA enzyme.Biochemistry371333013342CrossRefPubMedGoogle Scholar
  21. 21.
    Schultes, EA, Bartel, DP 2000One sequence, two ribozymes: Implications for the emergence of new ribozyme folds.Science289448452PubMedGoogle Scholar
  22. 22.
    Sleutels, F, Zwart, R, Barlow, DP 2002The non-coding Air RNA is required for silencing autosomal imprinted genes.Nature4157781PubMedGoogle Scholar
  23. 23.
    Sugimoto, N, Nakano, S, Katoh, M, Matsumura, A, Nakamuta, H, Ohmichi, T, Yoneyama, M, Sasaki, M 1995Thermodynamic parameters to predict stability of RNA/DNA hybrid duplexes.Biochemistry341121111216PubMedGoogle Scholar
  24. 24.
    Tang, J, Breaker, RR 2000Structural diversity of self-cleaving ribozymes.Proc Natl Acad Sci USA9757845789PubMedGoogle Scholar
  25. 25.
    Vanhee-Brossollet, C, Vaquero, C 1998Do natural antisense transcripts make sense in eukaryotes?Gene21119CrossRefPubMedGoogle Scholar
  26. 26.
    Wagner, EG, Simons, RW 1994Antisense RNA control in bacteria, phages, and plasmids.Annu Rev Microbiol48713742CrossRefPubMedGoogle Scholar
  27. 27.
    Wright, MC, Joyce, GF 1997Continuous in vitro evolution of catalytic function.Science276614617PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 2003

Authors and Affiliations

  1. 1.Departments of Chemistry and Molecular Biology and The Skaggs Institute for Chemical BiologyThe Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037USA

Personalised recommendations