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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 May 1;90(9):3806–3810. doi: 10.1073/pnas.90.9.3806

Sequence-specific recognition of double helical RNA and RNA.DNA by triple helix formation.

H Han 1, P B Dervan 1
PMCID: PMC46394  PMID: 7683407

Abstract

The stabilities of eight triple helical pyrimidine.purine.pyrimidine structures comprised of identical sequence but different RNA (R) or DNA (D) strand combinations were measured by quantitative affinity cleavage titration. The differences in equilibrium binding affinities reveal the importance of strand composition. For the sequences studied here, the stabilities of complexes containing a pyrimidine third strand D or R and purine.pyrimidine double helical DD, DR, RD, and RR decrease in order: D + DD, R + DD, R + DR, D + DR > R + RD, R + RR >> D + RR, D + RD (pH 7.0, 25 degrees C, 100 mM NaCl/1 mM spermine). These findings suggest that RNA and DNA oligonucleotides will be useful for targeting (i) double helical DNA and (ii) RNA.DNA hybrids if the purine Watson-Crick strand is DNA. However, RNA, but not DNA, oligonucleotides will be useful for sequence-specific binding of (i) double helical RNA and (ii) RNA.DNA hybrids if the purine Watson-Crick strand is RNA. This has implications for the design of artificial ligands targeted to specific sequences of double helical RNA and RNA.DNA hybrids.

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Selected References

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  1. Arnott S., Bond P. J., Selsing E., Smith P. J. Models of triple-stranded polynucleotides with optimised stereochemistry. Nucleic Acids Res. 1976 Oct;3(10):2459–2470. doi: 10.1093/nar/3.10.2459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arnott S., Chandrasekaran R., Millane R. P., Park H. S. DNA-RNA hybrid secondary structures. J Mol Biol. 1986 Apr 20;188(4):631–640. doi: 10.1016/s0022-2836(86)80011-0. [DOI] [PubMed] [Google Scholar]
  3. Beal P. A., Dervan P. B. Second structural motif for recognition of DNA by oligonucleotide-directed triple-helix formation. Science. 1991 Mar 15;251(4999):1360–1363. doi: 10.1126/science.2003222. [DOI] [PubMed] [Google Scholar]
  4. Chou S. H., Flynn P., Reid B. High-resolution NMR study of a synthetic DNA-RNA hybrid dodecamer containing the consensus pribnow promoter sequence: d(CGTTATAATGCG).r(CGCAUUAUAACG). Biochemistry. 1989 Mar 21;28(6):2435–2443. doi: 10.1021/bi00432a014. [DOI] [PubMed] [Google Scholar]
  5. Cooney M., Czernuszewicz G., Postel E. H., Flint S. J., Hogan M. E. Site-specific oligonucleotide binding represses transcription of the human c-myc gene in vitro. Science. 1988 Jul 22;241(4864):456–459. doi: 10.1126/science.3293213. [DOI] [PubMed] [Google Scholar]
  6. Iverson B. L., Dervan P. B. Adenine specific DNA chemical sequencing reaction. Nucleic Acids Res. 1987 Oct 12;15(19):7823–7830. doi: 10.1093/nar/15.19.7823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Johnston R. F., Pickett S. C., Barker D. L. Autoradiography using storage phosphor technology. Electrophoresis. 1990 May;11(5):355–360. doi: 10.1002/elps.1150110503. [DOI] [PubMed] [Google Scholar]
  8. Le Doan T., Perrouault L., Praseuth D., Habhoub N., Decout J. L., Thuong N. T., Lhomme J., Hélène C. Sequence-specific recognition, photocrosslinking and cleavage of the DNA double helix by an oligo-[alpha]-thymidylate covalently linked to an azidoproflavine derivative. Nucleic Acids Res. 1987 Oct 12;15(19):7749–7760. doi: 10.1093/nar/15.19.7749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Macaya R., Wang E., Schultze P., Sklenár V., Feigon J. Proton nuclear magnetic resonance assignments and structural characterization of an intramolecular DNA triplex. J Mol Biol. 1992 Jun 5;225(3):755–773. doi: 10.1016/0022-2836(92)90399-5. [DOI] [PubMed] [Google Scholar]
  10. Maher L. J., 3rd, Wold B., Dervan P. B. Inhibition of DNA binding proteins by oligonucleotide-directed triple helix formation. Science. 1989 Aug 18;245(4919):725–730. doi: 10.1126/science.2549631. [DOI] [PubMed] [Google Scholar]
  11. Milligan J. F., Groebe D. R., Witherell G. W., Uhlenbeck O. C. Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates. Nucleic Acids Res. 1987 Nov 11;15(21):8783–8798. doi: 10.1093/nar/15.21.8783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Moser H. E., Dervan P. B. Sequence-specific cleavage of double helical DNA by triple helix formation. Science. 1987 Oct 30;238(4827):645–650. doi: 10.1126/science.3118463. [DOI] [PubMed] [Google Scholar]
  13. Radhakrishnan I., de los Santos C., Patel D. J. Nuclear magnetic resonance structural studies of intramolecular purine.purine.pyrimidine DNA triplexes in solution. Base triple pairing alignments and strand direction. J Mol Biol. 1991 Oct 20;221(4):1403–1418. [PubMed] [Google Scholar]
  14. Rajagopal P., Feigon J. NMR studies of triple-strand formation from the homopurine-homopyrimidine deoxyribonucleotides d(GA)4 and d(TC)4. Biochemistry. 1989 Sep 19;28(19):7859–7870. doi: 10.1021/bi00445a048. [DOI] [PubMed] [Google Scholar]
  15. Roberts R. W., Crothers D. M. Stability and properties of double and triple helices: dramatic effects of RNA or DNA backbone composition. Science. 1992 Nov 27;258(5087):1463–1466. doi: 10.1126/science.1279808. [DOI] [PubMed] [Google Scholar]
  16. Rougée M., Faucon B., Mergny J. L., Barcelo F., Giovannangeli C., Garestier T., Hélène C. Kinetics and thermodynamics of triple-helix formation: effects of ionic strength and mismatches. Biochemistry. 1992 Sep 29;31(38):9269–9278. doi: 10.1021/bi00153a021. [DOI] [PubMed] [Google Scholar]
  17. Singleton S. F., Dervan P. B. Influence of pH on the equilibrium association constants for oligodeoxyribonucleotide-directed triple helix formation at single DNA sites. Biochemistry. 1992 Nov 17;31(45):10995–11003. doi: 10.1021/bi00160a008. [DOI] [PubMed] [Google Scholar]
  18. Strobel S. A., Dervan P. B. Single-site enzymatic cleavage of yeast genomic DNA mediated by triple helix formation. Nature. 1991 Mar 14;350(6314):172–174. doi: 10.1038/350172a0. [DOI] [PubMed] [Google Scholar]
  19. Strobel S. A., Doucette-Stamm L. A., Riba L., Housman D. E., Dervan P. B. Site-specific cleavage of human chromosome 4 mediated by triple-helix formation. Science. 1991 Dec 13;254(5038):1639–1642. doi: 10.1126/science.1836279. [DOI] [PubMed] [Google Scholar]
  20. Wang A. H., Fujii S., van Boom J. H., van der Marel G. A., van Boeckel S. A., Rich A. Molecular structure of r(GCG)d(TATACGC): a DNA--RNA hybrid helix joined to double helical DNA. Nature. 1982 Oct 14;299(5884):601–604. doi: 10.1038/299601a0. [DOI] [PubMed] [Google Scholar]

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