The Hairpin Elements of Nucleic Acid Structure: DNA and RNA Folding

  • C. W. Hilbers
  • H. A. Heus
  • M. J. P. van Dongen
  • S. S. Wijmenga
Part of the Nucleic Acids and Molecular Biology book series (NUCLEIC, volume 8)


Hairpin molecules have attracted a great deal of interest for many years. On one hand, this is because of their role in cellular processes, the recognition between the codon on mRNA and the anti-codon loop of tRNA being the most outstanding example. On the other hand, the study of the folding in hairpin loops and the thermodynamic parameters governing hairpin formation has been considered as a basis for the description of the stereochemistry of folding in more complicated nucleic acid structures and for the prediction of the secondary structure and its stability in such molecules.


Hairpin Loop Sharp Turn Anticodon Loop Nucleic Acid Structure Loop Residue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adhin MR, Alblas J, van Duin J (1990) Secondary structure at the 3′-terminal region of RNA coliphages: comparison with tRNA. Biochem Biophys Acta 1050:110–118PubMedGoogle Scholar
  2. Antao VP, Tinoco I Jr (1992) Thermodynamic parameters for loop formation in RNA and DNA hairpin tetraloops. Nucleic Acids Res 20:819–824PubMedCrossRefGoogle Scholar
  3. Antao VP, Lai SY, Tinoco I Jr (1991) A thermodynamic study of unusually stable RNA and DNA hairpins. Nucleic Acids Res 19:5901–5905PubMedCrossRefGoogle Scholar
  4. Benight AS, Schurr JM, Flynn PF, Reid BR, Wemmer DE (1988) Melting of a self-complementary DNA minicircle. Comparison of optical melting with exchange broadening of the nuclear magnetic resonance spectrum. J Mol Biol 200:377–399PubMedCrossRefGoogle Scholar
  5. Blommers MJJ (1990) NMR studies of loopfolding in a DNA hairpin molecule. An investigation of the solution structure of d(ATCCTA-TTTT-TAGGAT). In: Aspects of loopfolding in DNA hairpins. Thesis University of Nijmegen, Nijmegen, The Netherlands, pp 79–106Google Scholar
  6. Blommers MJJ, Haasnoot CAG, Hilbers CW, van Boom JH, van der Marel GA (1987) NMR studies of loopfolding in a DNA hairpin molecule. In: Nicolini C (ed) Structure and dynamics of biopolymers. NATO ASI Series E: Applied Sciences No 133. Martinus Nijhoff, Boston, pp 78–91Google Scholar
  7. Blommers MJJ, Walters JALI, Haasnoot CAG, Aelen JMA, van der Marel GA, van Boom JH, Hilbers CW (1989) Effects of base sequence on the loop folding in DNA hairpins. Biochemistry 28:7491–7498PubMedCrossRefGoogle Scholar
  8. Blommers MJJ, van de Ven FJM, van der Marel GA, van Boom JH, Hilbers CW (1991) The three-dimensional structure of a DNA hairpin in solution. Two-dimensional NMR studies and structural analysis of d(ATCCTATTTATAGGAT). Eur J Biochem 201: 33–51PubMedCrossRefGoogle Scholar
  9. Boulard Y, Gabarro-Arpa J, Cognet JAH, Le Bret M, Guy A, Teoule R, Guschlbauer W, Fazakerley GV (1991) The solution structure of a DNA hairpin containing a loop of three thymidines determined by nuclear magnetic resonance and molecular mechanics. Nucleic Acids Res 19:5159–5167PubMedCrossRefGoogle Scholar
  10. Breslauer KJ, Frank R, Blöcker H, Marky LA (1986) Predicting DNA duplex stability from the base sequence. Proc Natl Acad Sci USA 83:3746–3750PubMedCrossRefGoogle Scholar
  11. Chattopadhyaya R, Ikuta S, Grzeskowiak K, Dickerson RE (1988) X-ray structure of a DNA hairpin molecule. Nature 334:175–179PubMedCrossRefGoogle Scholar
  12. Chattopadhyaya R, Grzeskowiak K, Dickerson RE (1990) Structure of a T4 hairpin loop on a Z-DNA stem and comparison with A-RNA and B-DNA loops. J Mol Biol 211:189–210PubMedCrossRefGoogle Scholar
  13. Cheong C, Varani G, Tinoco I Jr (1990) Solution structure of an unusually stable RNA hairpin, 5′GGAC(UUCG)GUCC. Nature 346:680–682PubMedCrossRefGoogle Scholar
  14. D’Aubenton Carafa Y, Brody E, Thermes C (1990) Prediction of Rho-independent Escherichia coli transcription terminators. A statistical analysis of their stem-loop structures. J Mol Biol 216:835–858PubMedCrossRefGoogle Scholar
  15. Davis PW, Thurmes W, Tinoco I Jr (1993) Structure of a small hairpin. Nucleic Acids Res 21:537–545PubMedCrossRefGoogle Scholar
  16. Diekman S et al. (1989) Definitions and nomenclature of nucleic acid structure parameters EMBO J 8:1–4Google Scholar
  17. Erie DA, Suri AK, Breslauer KJ, Jones RA, Olson WK (1993) Theoretical predictions of DNA hairpin loop conformations: correlations with thermodynamic and spectroscopic data. Biochemistry 32:436–454PubMedCrossRefGoogle Scholar
  18. Garcia AE, Gupta G, Sarma MH, Sarma RH (1988) Stability and motion of a hairpin and the corresponding mismatched duplex: a theoretical exploration using molecular mechanics and normal analysis of 2D NMR results on d(GCCGCAGC). J Biomol Struct Dyn 6:525–542PubMedGoogle Scholar
  19. Germann MW, Kalisch BW, Lundberg P, Vogel HJ, van de Sande JH (1990) Perturbation of DNA hairpins containing the EcoRI recognition site by hairpin loops of varying size and composition: physical (NMR and UV) and enzymatic (EcoRI) studies. Nucleic Acids Res 18:1489–1498PubMedCrossRefGoogle Scholar
  20. Gralla J, Crothers DM (1973) Free energy of imperfect nucleic acid helices. II Small hairpin loops. J Mol Biol 73:497–511PubMedCrossRefGoogle Scholar
  21. Groebe DR, Uhlenbeck OC (1988) Characterization of RNA hairpin loop stability. Nucleic Acids Res 16:11725–11735PubMedCrossRefGoogle Scholar
  22. Gupta G, Sarma MH, Sarma RH, Bald R, Engelke U, Oei SL, Gessner R, Erdmann VA (1987) DNA hairpin structures in solution: 500MHz two-dimensional 1H NMR studies on d(CGCCGCAGC) and d(CGCCGTAGC). Biochemistry 26:7715–7723PubMedCrossRefGoogle Scholar
  23. Gutell RR, Weiser B, Woese CR, Noller HF (1985) Comparative anatomy of 16S-like ribosomal RNA. Prog Nucleic Acids Res Mol Biol 32:155–216CrossRefGoogle Scholar
  24. Haasnoot CAG, den Hartog JHJ, de Rooij JMF, van Boom JH, Altona C (1979) Local destabilisation of a DNA double helix by a T-T wobble pair. Nature 281:235–236PubMedCrossRefGoogle Scholar
  25. Haasnoot CAG, den Hartog JHJ, de Rooij JMF, van Boom JH, Altona C (1980) Loopstructures in synthetic oligodeoxynucleotides. Nucleic Acids Res 8:169–181PubMedCrossRefGoogle Scholar
  26. Haasnoot CAG, de Bruin SH, Berendsen RG, Janssen HGJM, Binnendijk TJJ, Hilbers CW, van der Marel GA, van Boom JH (1983) Structure, kinetics and thermodynamics of DNA hairpin fragments in solution. J Biomol Struct Dyn 1:115–129PubMedGoogle Scholar
  27. Haasnoot CAG, Hilbers CW, van der Marel GA, van Boom JH, Singh UC, Pattabiraman N, Kollman PA (1986) On loopfolding in nucleic acid hairpin-type structures. J Biomol Struct Dyn 3:843–857PubMedGoogle Scholar
  28. Haasnoot CAG, Blommers MJJ, Hilbers CW (1987) Conformational aspects of hairpin loops in DNA oligonucleotides. In: Ehrenberg A, Rigler R, Graslund A, Nilsson L (eds) Structure, dynamics and function of biomolecules. Springer Ser Biophys 1:212–216Google Scholar
  29. Hare DR, Reid BR (1986) Three-dimensional structure of a DNA hairpin in solution: two-dimensional NMR studies and distance geometry calculations on d(CGCGTTTTCGCG). Biochemistry 25:5341–5350PubMedCrossRefGoogle Scholar
  30. Harvey SC, Luo J, Lavery R (1988) DNA stem-loop structures in oligopurine-oligopyrimidine triplexes. Nucleic Acids Res 16:11795–11809PubMedCrossRefGoogle Scholar
  31. Heus HA, Pardi A (1991) Structural features that give rise to the unusual stability for RNA hairpins contaning GNRA loops. Science 253:191–194PubMedCrossRefGoogle Scholar
  32. Heus HA, Van Kimmenade JMA, Van Knippenberg PH, Hinz HJ (1983) Calorimetric measurements of the destabilization of a ribosomal RNA hairpin by dimethylation of two adjacent adenosines Nucleic Acids Res 11:203–210PubMedCrossRefGoogle Scholar
  33. Hilbers CW, Haasnoot CAG, de Bruin SH, Joordens JJM, van der Marel GA, van Boom JH (1985) Hairpin formation in synthetic oligonucleotides. Biochimie 67:685–695PubMedCrossRefGoogle Scholar
  34. Hilbers CW, Blommers MJJ, Haasnoot CAG, van der Marel GA, van Boom JH (1987) Structure and folding of RNA and DNA hairpins. Fresenius’ Z Anal Chem 327:70–71CrossRefGoogle Scholar
  35. Hilbers CW, Blommers MJJ, van de Ven FJM, van Boom JH, van der Marel GA (1989) Aspects of folding in nucleic acids. High resolution NMR studies. In: Lavery R, Olson WK, Westhof E (eds) CECAM Workshop: Nucleic acids and the information they convey: modelling sequence effects on the conformation, flexibility and interactions of DNA, pp 28–36Google Scholar
  36. Hilbers CW, Blommers MJJ, van de Ven FJM, van Boom JH, van der Marel GA (1991) High resolution NMR studies of DNA hairpins with four nucleotides in the loop region. Nucleosides Nucleotides 10:61–80CrossRefGoogle Scholar
  37. Hingerty B, Brown RS, Jack A (1978) Further refinement of the structure of Yeast tRNAPhe. J Mol Biol 124:523–534PubMedCrossRefGoogle Scholar
  38. Hiroa I, Nishimura Y, Naraoka T, Watanabe K, Arata Y, Miura K (1989) Extraordinarily stable structure of short single-stranded DNA fragments contain a specific base sequence d(GCGAAAGCG). Nucleic Acids Res 17:2223–2231CrossRefGoogle Scholar
  39. Holbrook SR, Sussman JL, Warrant RW, Kim SH (1978) Crystal structure of yeast phenylalanine transfer RNA. IL Structural features and functional implications. J Mol Biol 123:631–660PubMedCrossRefGoogle Scholar
  40. Holbrook SR, Cheong C, Tinoco I Jr, Kim SH (1991) Christal structure of an RNA double helix incorporating a track of non Watson-Crick base pairs. Nature 353:579–581PubMedCrossRefGoogle Scholar
  41. Ippel JH, Lanzotti V, Galeone A, Mayol L, van den Boogaart JE, Pikkemaat JA, Altona C (1992) An NMR study of the conformation and thermodynamics of the circular dumbbell d(pCGC-TT-GCG-TT). J Biomol Struct Dyn 9:821–836PubMedGoogle Scholar
  42. James JK, Tinoco I Jr (1993) The solution structure of a d[CTTCG)G] DNA hairpin and comparison to the unusually stable RNA analogue. Nucleic Acids Res 21:3287–3293PubMedCrossRefGoogle Scholar
  43. Jaquir A, Michell F (1987) Multiple exon-binding sites in Class II self-splicing introns. Cell 50:17–29CrossRefGoogle Scholar
  44. Kang CH, Zhang X, Rutcliff R, Moyzes R, Rich A (1992) Crystal structure of four-stranded Oxytricha telomeric DNA. Nature 356:126–131PubMedCrossRefGoogle Scholar
  45. Marky NL, Olson WK (1982) Loop formation in polynucleotides chains. I. Theory of hairpin loop closure. Biopolymers 21:2329–2344CrossRefGoogle Scholar
  46. Marky NL, Olson WK (1987) Loop formation in polynucleotide chains. II. Flexibility of the anticodon loop of tRNAPhe. Biopolymers 26:415–438PubMedCrossRefGoogle Scholar
  47. Marky LA, Blumenfeld KS, Kozlowski S, Breslauer KJ (1983) Salt-dependent conformational transitions in the self-complementary nucleotide d(CGCG-AATT-CGCG): evidence for hairpin formation. Biopolymers 22:1247–1459PubMedCrossRefGoogle Scholar
  48. Mooren MMW, Pulleyblank DE, Wijmenga SS, Blommers MJJ, Hilbers CW (1990) Polypurine/polypyrimidine hairpins form a triple helix structure at low pH. Nucleic Acids Res 18:6523–6529PubMedCrossRefGoogle Scholar
  49. Mooren MMW, Pulleyblank DE, Wijmenga SS, Hilbers CW (1993a) The solution structure of the hairpin formed by d(TCTCTC-TTT-GAGAGA) (to be published)Google Scholar
  50. Mooren MMW, Willems EFA, Wijmenga SS, van der Marel GA, van Boom JH, Hilbers CW (1993b) Structural features of the DNA hairpin d(ATCCTA-GTTA-TAGGAT) (to be published)Google Scholar
  51. Moras D, Comarmond MB, Fischer J, Weiss R, Thierry JC (1980) Crystal structure of yeast tRNAAsp. Nature 288:669–674PubMedCrossRefGoogle Scholar
  52. Orbons LPM, van der Marel GA, van Boom JH, Altona C (1986) Hairpin and duplex formation of the DNA octamer d(m5C-G-m5G-T-G-m5C-G) in solution. An NMR study. Nucleic Acids Res 14:4187–4196PubMedCrossRefGoogle Scholar
  53. Orbons LPM, van der Marel GA, van Boom JH, Altona C (1987a) An NMR study of the polymorphous behavior of the mismatched DNA octamer d(m5C-G-m5G-T-G-m5C-G) in solution. The B, Z, and hairpin forms. J Biomol Struct Dyn 4:939–963PubMedGoogle Scholar
  54. Orbons LPM, van Beuzekom AA, Altona C (1987b) Conformational and model-building studies of the hairpin form of the mismatched DNA octamer d(m5C-G-m5G-T-G-m5C-G). J Biomol Struct Dyn 4:965–987PubMedGoogle Scholar
  55. Pace NR, Smith DK, Olsen GJ, James BD (1989) Phylogenetic comparative analysis and the secondary structure of ribonuclease P RNA — a review. Gene 82:65–75PubMedCrossRefGoogle Scholar
  56. Paner TM, Amaratunga M, Doktycz MJ, Benight AS (1990) Analysis of melting of the DNA hairpins formed from the oligomer sequences d[GGATA(X4)GTATCC] (X = A, T, G, C). Biopolymers 29:1715–1734PubMedCrossRefGoogle Scholar
  57. Pieters JLM, de Vroom E, van der Marel GA, van Boom JH, Koning TMG, Kaptein R, Altona C (1990) Hairpin structures in DNA containing arabinofuranosylcytosine. A combination of nuclear magnetic resonance and molecular dynamics. Biochemistry 29:788–799PubMedCrossRefGoogle Scholar
  58. Poritz MA, Strub K, Walter P (1988) Human SRP RNA and E. coli 4.5S RNA containing a highly homologous structural domain. Cell 55:4–6PubMedCrossRefGoogle Scholar
  59. Puglisi JD, Wyatt JR, Tinoco I Jr (1990) Solution conformation of an RNA hairpin loop. Biochemistry 29:4215–4226PubMedCrossRefGoogle Scholar
  60. Rackowsky S, Scheraga HA (1978) Differential geometry and polymer conformation. 1. Comparison of protein conformations. Macromolecules 11:1168–1174CrossRefGoogle Scholar
  61. Saenger W (1984) Principles of nucleic acid structure. Springer, Berlin Heidelberg New YorkCrossRefGoogle Scholar
  62. SantaLucia J Jr, Ryszard K, Turner DH (1992) Context dependence of hydrogen bond free energy revealed by substitutions in an RNA hairpin. Science 256:217–219PubMedCrossRefGoogle Scholar
  63. Sarma MH, Gupta G, Sarma RH, Rald R, Engelke U, Oei SL, Gessner R, Erdmann VA (1987) DNA structures in which an adenine-cytosine mismatch pair forms an integral part of the double helix. Biochemistry 26:7707–7715PubMedCrossRefGoogle Scholar
  64. Scheffler IE, Elson EL, Baldwin RL (1968) Helix formation by dAT oligomers. I. Hairpin and straight-chain helices. J Mol Biol 36:291–304PubMedCrossRefGoogle Scholar
  65. Senior MM, Jones RA, Breslauer KJ (1988) Influence of loop residues on the relative stabilities of DNA hairpin structures. Proc Natl Acad Sci USA 85:6242–6246PubMedCrossRefGoogle Scholar
  66. Sussman JL, Holbrook SR, Warrant RW, Church GM, Kim SH (1978) Crystal structure of yeast phenylalanine transfer RNA. I. Crystallographic refinement. J Mol Biol 123: 607–630PubMedCrossRefGoogle Scholar
  67. Tuerk C, Gauss P, Thermes C, Groebe DR, Gayle M, Guild N, Stormo G, ďAubenton-Carafa Y, Uhlenbeck OC, Tinoco I Jr, Brody EN, Gold L (1988) CUUCGG hairpins: extraordinarily stable RNA secondary structures associated with various biochemical processes. Proc Natl Acad Sci USA 85:1364–1368PubMedCrossRefGoogle Scholar
  68. Turner DH, Sugimoto N, Freier SM (1988) RNA structure prediction. Annu Rev Biophys Biophys Chem 17:167–192PubMedCrossRefGoogle Scholar
  69. Turner DH, Sugimoto N, Freier SM (1990) Thermodynamics and kinetics of base pairing of DNA and RNA self-assembly and helix coil transition. In: Landolt-Börnstein, vol 1. Nucleic acids. Group 7: Biophysics. Springer, Berlin Heidelberg New York, pp 201–227Google Scholar
  70. Uhlenbeck OC, Borer PN, Dengler B, Tinoco I Jr (1973) Stability of RNA hairpin loops: A6-Cm-U6. J Mol Biol 73:483–496PubMedCrossRefGoogle Scholar
  71. Van Charldorp R, Heus HA, Van Knippenberg PH, Joordens J, Den Bruin SH, Hilbers CWH (1981) Destabilization of secondary structure in 16S ribosomal RNA by dimethylation of two adjacent adenosins. Nucleic Acids Res 9:4413–4422PubMedCrossRefGoogle Scholar
  72. Van Knippenberg PH (1986) Structural and functional aspects of the N6,N6 dimethy-ladenosines in 16S ribosomal RNA. In: Hadesty B, Kramer G (eds) Structure, function and genetics of ribosomes. Springer, Berlin Heidelberg New York, pp 412–424Google Scholar
  73. Varani G, Tinoco I Jr (1991) RNA structure and NMR spectroscopy. Q Rev Biophys 24:479–532PubMedCrossRefGoogle Scholar
  74. Varani G, Cheong C, Tinoco I Jr (1991) Structure of an unusually stable hairpin. Biochemistry 30:3280–3289PubMedCrossRefGoogle Scholar
  75. Waring RB, Davies RW (1984) Assessment of a model for intron RNA secondary structure relevant to RNA self-splicing — a review. Gene 28:277–291PubMedCrossRefGoogle Scholar
  76. Wemmer DE, Chou SH, Hare DR, Reid BR (1985) Duplex-hairpin transitions in DNA: NMR studies on CGCGTATAGCG. Nucleic Acids Res 13:3755–3772PubMedCrossRefGoogle Scholar
  77. Westhof E, Sundaralingam M (1986) Restrained refinement of the monoclinic form of yeast phenylalanine transfer RNA. Temperature factors and dynamics, coordinated waters, and base-pair propeller twist angles. Biochemistry 25:4868–4878PubMedCrossRefGoogle Scholar
  78. Westhof E, Dumas P, Moras D (1985) Crystallographic refiment of Yeast Aspartic Acid Transfer RNA. J Mol Biol 184:119–145PubMedCrossRefGoogle Scholar
  79. Williamson JR, Boxer SG (1989a) Multinuclear NMR studies of DNA hairpins. 1. Structure and dynamics of d(CGCGTTGTTCGCG). Biochemistry 28:2819–2831PubMedCrossRefGoogle Scholar
  80. Williamson JR, Boxer SG (1989b) Multinuclear NMR studies of DNA hairpins. 2. Sequence-dependent structural variations. Biochemistry 28:2831–2836PubMedCrossRefGoogle Scholar
  81. Woese CR, Gutell RR, Gupta R, Noller HF (1983) Detailed analysis of the higher order structure of 16S-like ribosomal riibonucleic acids. Microbiol Rev 47:621–669PubMedGoogle Scholar
  82. Woese CR, Winker S, Gutell RR (1990) Architecture of ribosomal RNA: constraints on the sequence with “tetra-loops”. Proc Natl Acad Sci USA 87:8467–8471PubMedCrossRefGoogle Scholar
  83. Wolk SK, Hardin CC, Germann MW, van de Sande JH, Tinoco I Jr (1988) Comparison of the B- and Z-form hairpin loop structures formed by d(CG)5T4(CG)5. Biochemistry 27:6960–6967PubMedCrossRefGoogle Scholar
  84. Xodo LE, Manzini G, Quadrofogio F, van der Marel GA, van Boom JH (1988) Oligodeoxynucleotide folding in solution: loop size and stability of B-hairpins. Biochemistry 27:6321–6326PubMedCrossRefGoogle Scholar
  85. Zhou N, Vogel HJ (1993) Two-dimensional NMR and restrained molecular dynamics studies of the hairpin d(T8C4A8): detection of an extraloop cytosine. Biochemistry 32:637–645PubMedCrossRefGoogle Scholar
  86. Zhou N, Germann MW, van de Sande JH, Pattabiraman N, Vogel HJ (1993) Solution structure of the parallel-stranded hairpin d(T8<>C4A8) as determined by two-dimensional NMR. Biochemistry 32:646–656PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • C. W. Hilbers
    • 1
  • H. A. Heus
    • 1
  • M. J. P. van Dongen
    • 1
  • S. S. Wijmenga
    • 1
  1. 1.NSR Center for Molecular Structure, Synthesis and Design. Laboratory of Biophysical ChemistryUniversity of NijmegenNijmegenThe Netherlands

Personalised recommendations