Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1997 Oct 15;25(20):4117–4122. doi: 10.1093/nar/25.20.4117

The crystal structure of an RNA oligomer incorporating tandem adenosine-inosine mismatches.

R J Carter 1, K J Baeyens 1, J SantaLucia 1, D H Turner 1, S R Holbrook 1
PMCID: PMC146998  PMID: 9321667

Abstract

The X-ray crystallographic structure of the RNA duplex [r(CGCAIGCG)]2 has been refined to 2.5 A. It shows a symmetric internal loop of two non-Watson-Crick base pairs which form in the middle of the duplex. The tandem A-I/I-A pairs are related by a crystallographic two-fold axis. Both A(anti)-I(anti) mismatches are in a head-to-head conformation forming hydrogen bonds using the Watson-Crick positions. The octamer duplexes stack above one another in the cell forming a pseudo-infinite helix throughout the crystal. A hydrated calcium ion bridges between the 3'-terminal of one molecule and the backbone of another. The tandem A-I mismatches are incorporated with only minor distortion to the backbone. This is in contrast to the large helical perturbations often produced by sheared G-A pairs in RNA oligonucleotides.

Full Text

The Full Text of this article is available as a PDF (441.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baeyens K. J., De Bondt H. L., Holbrook S. R. Structure of an RNA double helix including uracil-uracil base pairs in an internal loop. Nat Struct Biol. 1995 Jan;2(1):56–62. doi: 10.1038/nsb0195-56. [DOI] [PubMed] [Google Scholar]
  2. Baeyens K. J., De Bondt H. L., Pardi A., Holbrook S. R. A curved RNA helix incorporating an internal loop with G.A and A.A non-Watson-Crick base pairing. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12851–12855. doi: 10.1073/pnas.93.23.12851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Battiste J. L., Mao H., Rao N. S., Tan R., Muhandiram D. R., Kay L. E., Frankel A. D., Williamson J. R. Alpha helix-RNA major groove recognition in an HIV-1 rev peptide-RRE RNA complex. Science. 1996 Sep 13;273(5281):1547–1551. doi: 10.1126/science.273.5281.1547. [DOI] [PubMed] [Google Scholar]
  4. Cate J. H., Gooding A. R., Podell E., Zhou K., Golden B. L., Kundrot C. E., Cech T. R., Doudna J. A. Crystal structure of a group I ribozyme domain: principles of RNA packing. Science. 1996 Sep 20;273(5282):1678–1685. doi: 10.1126/science.273.5282.1678. [DOI] [PubMed] [Google Scholar]
  5. Corfield P. W., Hunter W. N., Brown T., Robinson P., Kennard O. Inosine.adenine base pairs in a B-DNA duplex. Nucleic Acids Res. 1987 Oct 12;15(19):7935–7949. doi: 10.1093/nar/15.19.7935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cruse W. B., Aymani J., Kennard O., Brown T., Jack A. G., Leonard G. A. Refined crystal structure of an octanucleotide duplex with I.T. mismatched base pairs. Nucleic Acids Res. 1989 Jan 11;17(1):55–72. doi: 10.1093/nar/17.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davis B. D., Anderson P., Sparling P. F. Pairing of inosine with adenosine in codon position two in the translation of polyinosinic acid. J Mol Biol. 1973 May 15;76(2):223–232. doi: 10.1016/0022-2836(73)90386-0. [DOI] [PubMed] [Google Scholar]
  8. Gautheret D., Konings D., Gutell R. R. A major family of motifs involving G.A mismatches in ribosomal RNA. J Mol Biol. 1994 Sep 9;242(1):1–8. doi: 10.1006/jmbi.1994.1552. [DOI] [PubMed] [Google Scholar]
  9. Grzeskowiak K., Goodsell D. S., Kaczor-Grzeskowiak M., Cascio D., Dickerson R. E. Crystallographic analysis of C-C-A-A-G-C-T-T-G-G and its implications for bending in B-DNA. Biochemistry. 1993 Aug 31;32(34):8923–8931. doi: 10.1021/bi00085a025. [DOI] [PubMed] [Google Scholar]
  10. Gutell R. R., Weiser B., Woese C. R., Noller H. F. Comparative anatomy of 16-S-like ribosomal RNA. Prog Nucleic Acid Res Mol Biol. 1985;32:155–216. doi: 10.1016/s0079-6603(08)60348-7. [DOI] [PubMed] [Google Scholar]
  11. Holbrook S. R., Cheong C., Tinoco I., Jr, Kim S. H. Crystal structure of an RNA double helix incorporating a track of non-Watson-Crick base pairs. Nature. 1991 Oct 10;353(6344):579–581. doi: 10.1038/353579a0. [DOI] [PubMed] [Google Scholar]
  12. Kumar V. D., Harrison R. W., Andrews L. C., Weber I. T. Crystal structure at 1.5-A resolution of d(CGCICICG), an octanucleotide containing inosine, and its comparison with d(CGCG) and d(CGCGCG) structures. Biochemistry. 1992 Feb 11;31(5):1541–1550. doi: 10.1021/bi00120a035. [DOI] [PubMed] [Google Scholar]
  13. Leonard G. A., Booth E. D., Hunter W. N., Brown T. The conformational variability of an adenosine.inosine base-pair in a synthetic DNA dodecamer. Nucleic Acids Res. 1992 Sep 25;20(18):4753–4759. doi: 10.1093/nar/20.18.4753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Leonard G. A., McAuley-Hecht K. E., Ebel S., Lough D. M., Brown T., Hunter W. N. Crystal and molecular structure of r(CGCGAAUUAGCG): an RNA duplex containing two G(anti).A(anti) base pairs. Structure. 1994 Jun 15;2(6):483–494. doi: 10.1016/S0969-2126(00)00049-6. [DOI] [PubMed] [Google Scholar]
  15. Lietzke S. E., Barnes C. L., Berglund J. A., Kundrot C. E. The structure of an RNA dodecamer shows how tandem U-U base pairs increase the range of stable RNA structures and the diversity of recognition sites. Structure. 1996 Aug 15;4(8):917–930. doi: 10.1016/s0969-2126(96)00099-8. [DOI] [PubMed] [Google Scholar]
  16. Malim M. H., Hauber J., Le S. Y., Maizel J. V., Cullen B. R. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature. 1989 Mar 16;338(6212):254–257. doi: 10.1038/338254a0. [DOI] [PubMed] [Google Scholar]
  17. Martin F. H., Castro M. M., Aboul-ela F., Tinoco I., Jr Base pairing involving deoxyinosine: implications for probe design. Nucleic Acids Res. 1985 Dec 20;13(24):8927–8938. doi: 10.1093/nar/13.24.8927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pley H. W., Flaherty K. M., McKay D. B. Three-dimensional structure of a hammerhead ribozyme. Nature. 1994 Nov 3;372(6501):68–74. doi: 10.1038/372068a0. [DOI] [PubMed] [Google Scholar]
  19. Ravishanker G., Swaminathan S., Beveridge D. L., Lavery R., Sklenar H. Conformational and helicoidal analysis of 30 PS of molecular dynamics on the d(CGCGAATTCGCG) double helix: "curves", dials and windows. J Biomol Struct Dyn. 1989 Feb;6(4):669–699. doi: 10.1080/07391102.1989.10507729. [DOI] [PubMed] [Google Scholar]
  20. SantaLucia J., Jr, Kierzek R., Turner D. H. Effects of GA mismatches on the structure and thermodynamics of RNA internal loops. Biochemistry. 1990 Sep 18;29(37):8813–8819. doi: 10.1021/bi00489a044. [DOI] [PubMed] [Google Scholar]
  21. SantaLucia J., Jr, Kierzek R., Turner D. H. Stabilities of consecutive A.C, C.C, G.G, U.C, and U.U mismatches in RNA internal loops: Evidence for stable hydrogen-bonded U.U and C.C.+ pairs. Biochemistry. 1991 Aug 20;30(33):8242–8251. doi: 10.1021/bi00247a021. [DOI] [PubMed] [Google Scholar]
  22. SantaLucia J., Jr, Turner D. H. Structure of (rGGCGAGCC)2 in solution from NMR and restrained molecular dynamics. Biochemistry. 1993 Nov 30;32(47):12612–12623. doi: 10.1021/bi00210a009. [DOI] [PubMed] [Google Scholar]
  23. Scott W. G., Finch J. T., Klug A. The crystal structure of an all-RNA hammerhead ribozyme: a proposed mechanism for RNA catalytic cleavage. Cell. 1995 Jun 30;81(7):991–1002. doi: 10.1016/s0092-8674(05)80004-2. [DOI] [PubMed] [Google Scholar]
  24. Wimberly B. A common RNA loop motif as a docking module and its function in the hammerhead ribozyme. Nat Struct Biol. 1994 Nov;1(11):820–827. doi: 10.1038/nsb1194-820. [DOI] [PubMed] [Google Scholar]
  25. Wu M., McDowell J. A., Turner D. H. A periodic table of symmetric tandem mismatches in RNA. Biochemistry. 1995 Mar 14;34(10):3204–3211. doi: 10.1021/bi00010a009. [DOI] [PubMed] [Google Scholar]
  26. Wu M., SantaLucia J., Jr, Turner D. H. Solution structure of (rGGCAGGCC)2 by two-dimensional NMR and the iterative relaxation matrix approach. Biochemistry. 1997 Apr 15;36(15):4449–4460. doi: 10.1021/bi9625915. [DOI] [PubMed] [Google Scholar]
  27. Wu M., Turner D. H. Solution structure of (rGCGGACGC)2 by two-dimensional NMR and the iterative relaxation matrix approach. Biochemistry. 1996 Jul 30;35(30):9677–9689. doi: 10.1021/bi960133q. [DOI] [PubMed] [Google Scholar]
  28. Xuan J. C., Weber I. T. Crystal structure of a B-DNA dodecamer containing inosine, d(CGCIAATTCGCG), at 2.4 A resolution and its comparison with other B-DNA dodecamers. Nucleic Acids Res. 1992 Oct 25;20(20):5457–5464. doi: 10.1093/nar/20.20.5457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yuan H., Quintana J., Dickerson R. E. Alternative structures for alternating poly(dA-dT) tracts: the structure of the B-DNA decamer C-G-A-T-A-T-A-T-C-G. Biochemistry. 1992 Sep 1;31(34):8009–8021. [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES