Abstract
Homopyrimidine peptide nucleic acids (PNAs) form loop structures when binding to complementary double-stranded DNA by strand displacement, and we now show that RNA polymerase recognizes these and initiates RNA transcription from PNA/double-stranded DNA strand displacement complexes at an efficiency comparable to that of the strong Escherichia coli lacUV5 promoter. Thus PNA targets can be considered as artificial promoters controlled positively by the corresponding PNA as a transcription factor. Our results have implications for the mechanism of action of RNA polymerase and suggest the use of PNA as specific gene activating reagents and drugs.
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- Cherny D. Y., Belotserkovskii B. P., Frank-Kamenetskii M. D., Egholm M., Buchardt O., Berg R. H., Nielsen P. E. DNA unwinding upon strand-displacement binding of a thymine-substituted polyamide to double-stranded DNA. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1667–1670. doi: 10.1073/pnas.90.5.1667. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Daube S. S., von Hippel P. H. Functional transcription elongation complexes from synthetic RNA-DNA bubble duplexes. Science. 1992 Nov 20;258(5086):1320–1324. doi: 10.1126/science.1280856. [DOI] [PubMed] [Google Scholar]
- Giardina C., Lis J. T. DNA melting on yeast RNA polymerase II promoters. Science. 1993 Aug 6;261(5122):759–762. doi: 10.1126/science.8342041. [DOI] [PubMed] [Google Scholar]
- Hanvey J. C., Peffer N. J., Bisi J. E., Thomson S. A., Cadilla R., Josey J. A., Ricca D. J., Hassman C. F., Bonham M. A., Au K. G. Antisense and antigene properties of peptide nucleic acids. Science. 1992 Nov 27;258(5087):1481–1485. doi: 10.1126/science.1279811. [DOI] [PubMed] [Google Scholar]
- Kim J. L., Nikolov D. B., Burley S. K. Co-crystal structure of TBP recognizing the minor groove of a TATA element. Nature. 1993 Oct 7;365(6446):520–527. doi: 10.1038/365520a0. [DOI] [PubMed] [Google Scholar]
- Kim Y., Geiger J. H., Hahn S., Sigler P. B. Crystal structure of a yeast TBP/TATA-box complex. Nature. 1993 Oct 7;365(6446):512–520. doi: 10.1038/365512a0. [DOI] [PubMed] [Google Scholar]
- McClure W. R. Mechanism and control of transcription initiation in prokaryotes. Annu Rev Biochem. 1985;54:171–204. doi: 10.1146/annurev.bi.54.070185.001131. [DOI] [PubMed] [Google Scholar]
- Nielsen P. E., Egholm M., Berg R. H., Buchardt O. Peptide nucleic acids (PNAs): potential antisense and anti-gene agents. Anticancer Drug Des. 1993 Feb;8(1):53–63. [PubMed] [Google Scholar]
- Nielsen P. E., Egholm M., Berg R. H., Buchardt O. Sequence specific inhibition of DNA restriction enzyme cleavage by PNA. Nucleic Acids Res. 1993 Jan 25;21(2):197–200. doi: 10.1093/nar/21.2.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nielsen P. E., Egholm M., Berg R. H., Buchardt O. Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science. 1991 Dec 6;254(5037):1497–1500. doi: 10.1126/science.1962210. [DOI] [PubMed] [Google Scholar]
- Roeder R. G. The complexities of eukaryotic transcription initiation: regulation of preinitiation complex assembly. Trends Biochem Sci. 1991 Nov;16(11):402–408. doi: 10.1016/0968-0004(91)90164-q. [DOI] [PubMed] [Google Scholar]
- Travers A. A. Structure and function of E. coli promoter DNA. CRC Crit Rev Biochem. 1987;22(3):181–219. doi: 10.3109/10409238709101483. [DOI] [PubMed] [Google Scholar]
- von Hippel P. H., Bear D. G., Morgan W. D., McSwiggen J. A. Protein-nucleic acid interactions in transcription: a molecular analysis. Annu Rev Biochem. 1984;53:389–446. doi: 10.1146/annurev.bi.53.070184.002133. [DOI] [PubMed] [Google Scholar]