Skip to main content
Log in

The effect of secondary structure on cleavage of the phosphodiester bonds of RNA

  • Review Article
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

This review discusses the effects the secondary structure of an RNA molecule has on the inherent reactivity of its phosphodiester bonds, and on the catalytic activity of metal ion-based cleaving agents. The basic principles of the intramolecular transesterification of RNA phosphodiester bonds, particularly cleavage, are first briefly described. Studies of the structural effects on the cleavage, in the absence and in the presence of metal ion catalysts, are then reviewed, and the sources of the reactivity differences observed in different structures are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Oivanen, M., Kuusela, S., and Lönnberg, H. (1998) Kinetics and mechanisms for the cleavage and isomerization of the phosphodiester bonds of RNA by Brønsted acids and bases. Chem. Rev. 98, 961–990.

    Article  PubMed  CAS  Google Scholar 

  2. Perreault, P. M. and Anslyn, E. V. (1997) Unifying the current data on the mechanism of cleavage-transesterification of RNA. Angew. Chem. Int. Ed. Engl. 36, 432–450.

    Article  Google Scholar 

  3. Trawick, B. N., Daniher, A., and Bashkin, J. K. (1998) Inorganic mimics of ribonucleases and ribozymes: from random cleavage to sequence-specific chemistry to catalytic antisense drugs. Chem. Rev. 98, 939–960.

    Article  PubMed  CAS  Google Scholar 

  4. Zhou, D.-M. and Taira, K. (1998) The hydrolysis of RNA: From theoretical calculations to the hammerhead ribozyme-mediated cleavage of RNA. Chem. Rev. 98, 991–1026.

    Article  PubMed  CAS  Google Scholar 

  5. Cech, T., Zaugh, A. J., and Grabowski, P. J. (1981) In vitro splicing of the ribosomal RNA precursor of tetrahymena: involvement of a guanosine nucleotide in the excision of the intervening sequence. Cell 29, 487–496.

    Article  Google Scholar 

  6. Guerrier-Takada, C., Gardiener, K., Marsh, T., Pace N. and Altman, S. (1983) The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35, 849–857.

    Article  PubMed  CAS  Google Scholar 

  7. Pyle, A. M. (1996) Role of metal ions in ribozymes. Metal Ions Biol. Syst. 32, 479–520.

    CAS  Google Scholar 

  8. Bashkin, J. K., Sampath, U. and Frolova, E. (1995) Ribozyme mimics as catalytic antisense reagents. Appl. Biochem. Biotech. 54, 43–56.

    CAS  Google Scholar 

  9. Vlasov, V. V., S’ilnikov, V. N. and Zenkova, M. A. (1998) Chemical ribonucleases. Mol. Biol. 32, 50–57.

    CAS  Google Scholar 

  10. Komiyama, M. (1995) Sequence-specific and hydrolytic scission of DNA and RNA by lanthanide complex-oligoDNA hybrids. J. Biochem. 118, 665–670.

    PubMed  CAS  Google Scholar 

  11. De Mesmaeker, A., Häner, R., Martin, P. and Moser, H. (1995) Antisense oligonucleotides. Acc. Chem. Res. 28, 366–374.

    Article  Google Scholar 

  12. Häner, R., Hall, J., Pfutzer, A. and Husken, D. (1998) Development of artificial ribonucleases. Pure Appl. Chem. 70, 111–116.

    Google Scholar 

  13. Sigman, D. S., Bruice, T. W., Mazumder, A. and Sutton, C. L. (1993) Targeted chemical nucleases. Acc. Chem. Res. 26, 98–104.

    Article  CAS  Google Scholar 

  14. Duarte, V., Sixou, S., Favre, G., Pratviel, G. and Meunier, B. (1997) Oxidative damage on RNA mediated by cationic metalloporphyrin antisense oligonucleotide conjugates. J. Chem. Soc. Dalton Trans. 21, 4113–4118.

    Article  Google Scholar 

  15. Bashkin, J. K. and Jenkins, L. A. (1994) The role of metal ions in the hydrolytic cleavage of DNA and RNA. Comments Inorg. Chem. 16, 77–93.

    Article  CAS  Google Scholar 

  16. Kuusela, S. and Lönnberg, H. (1996) Effect of metal ions on the hydrolytic reactions of nucleosides and their phosphoesters. Metal Ions Biol. Syst. 32, 272–300.

    Google Scholar 

  17. Kuusela, S. and Lönnberg, H. (1997) Metal ion dependent hydrolysis of RNA. Curr. Topics Sol. Chem. 2, 29–47.

    CAS  Google Scholar 

  18. Morrow, J. R. (1996) Hydrolytic cleavage of RNA catalysed by metal ion complexes. Metal Ions Biol. Syst. 33, 561–592.

    CAS  Google Scholar 

  19. Blaskó, A. and Bruice, T. C. (1999) Recent studies of nucleophilic, general-acid, and metal ion catalysis of phosphate diester hydrolysis. Acc. Chem. Res. 32, 475–484.

    Article  Google Scholar 

  20. Williams, N. H., Takasaki, B., Wall, M. and Chin, J. (1999) Structure and nuclease activity of simple dinuclear metal complexes: quantitative dissection of the role of metal ions. Acc. Chem. Res. 32, 485–493.

    Article  CAS  Google Scholar 

  21. Daniher, A. T. and Bashkin, J. K. (1998) Precise control of RNA cleavage by ribozyme mimics. Chem. Commun. 1077–1078.

  22. Bashkin, J. K., Frolova, E. and Sampath, U. (1994) Sequence-specific cleavage of HIV mRNA by a ribozyme mimic. J. Am. Chem. Soc. 116, 5981–5982.

    Article  CAS  Google Scholar 

  23. Magda, D., Crofts, S., Lin, A., Miles, D., Wright, M. and Sessler, J. L. (1997) Synthesis and kinetic properties of ribozyme analogues prepared using phosphoramidate derivatives of dysprosium(III) texapyrin. J. Am. Chem. Soc. 119, 2293–2294.

    Article  CAS  Google Scholar 

  24. Matsuda, S., Ishikubo, A., Kuzuya, A., Yashiro, M. and Komiyama, M. (1998) Conjugates of a dinuclear zinc(II) complex and DNA oligomers as novel sequence-selective artificial ribonucleases. Angew. Chem. Int. Edit. Engl. 37, 3284–3286.

    Article  CAS  Google Scholar 

  25. Hall, J., Husken, D., Pieles, U., Moser, H. E. and Häner, R. (1994) Efficient sequence-specific cleavage of RNA using novel europium complexes conjugated to oligonucleotides. Chem. Biol. 1, 185–190.

    Article  PubMed  CAS  Google Scholar 

  26. Inoue, H., Furukawa, T., Shimizu, T., Tamura, T., Matsui, M. and Ohtsuka, E. (1999) Efficient site-specific cleavage of RNA using a terpyridine-copper(II) complex joined to a 2′-O-methyloligonucleotide by a non-flexible linker. Chem. Commun. 45–46.

  27. Hovinen, J., Guzaev, A., Azhayeva, E., Azhayev, A. and Lönnberg, H. (1995) Imidazole tethered oligodeoxyribonucleotides: synthesis and RNA cleaving activity. J. Org. Chem. 60, 2205–2209.

    Article  CAS  Google Scholar 

  28. Nicholson, A. W. (1996) Structure, reactivity and biology of double-stranded RNA. Prog. Nucleic Acid Res. Mol. Biol., 52, 1–56.

    Article  PubMed  CAS  Google Scholar 

  29. Kierzek, R. (1992) Nonenzymatic hydrolysis of oligoribonucleotides. Nucleic Acids Res. 20, 5079–5084.

    Article  PubMed  CAS  Google Scholar 

  30. Kolasa, K. A., Morrow, J. R., and Sharma, A. P. (1993) Trivalent lanthanide ions do not cleave RNA in DNA-RNA hybrids. Inorg. Chem. 32, 3983–3984.

    Article  CAS  Google Scholar 

  31. Hüsken, D., Goodall, G., Blommers, M. J. J., Jahnke, W., Hall, J., Häner, R. and Moser, H. E. (1996) Creating RNA bulges: cleavage of RNA in RNA/DNA duplexes by metal ion catalysis. Biochemistry 35, 16591–16600.

    Article  PubMed  Google Scholar 

  32. Zagorowska, I., Kuusela, S. and Lönnberg, H. (1998) Metal ion-dependent hydrolysis of RNA phosphodiester bonds within hairpin loops. A comparative kinetic study on chimeric ribo/2′-O-methylribo oligoribonucleotides. Nucleic Acids Res. 26, 3392–3396.

    Article  PubMed  CAS  Google Scholar 

  33. Cuchillo, C. M., Pares, X., Guasch, A., Barman, T., Travers, F. and Nogues, M. V. (1993) The role of 2′,3′-cyclic phosphodiesters in the bovine pancreatic ribonuclease A catalysed cleavage of RNA: Intermediates or products. FEBS Lett. 333, 207–210.

    Article  PubMed  CAS  Google Scholar 

  34. Loll, P. and Lattman, E. E. (1989) The crystal structure of the ternary complex of staphylococcal nuclease, calcium, and the inhibitor pdTp. Proteins Struct. Funct. Genet. 5, 183–201.

    Article  PubMed  CAS  Google Scholar 

  35. Zagórowska, I., Mikkola, S. and Lönnberg, H. (1999) Hydrolysis of phosphodiester bonds within hairpin loops in buffer solutions: the effect of secondary structure on the inherent reactivity of RNA phosphodiester bonds. Helv. Chim. Acta 82, 2105–2111.

    Article  Google Scholar 

  36. Brown, R. S., Dewan, J. C. and Klug, A. (1985) Crystallographic and biochemical investigation of the lead(II)-catalyzed hydrolysis of yeast phenylalanine tRNA. Biochemistry 24, 4785–4801.

    Article  PubMed  CAS  Google Scholar 

  37. Sundaralingam, M., Rubin, J. R. and Cannon, J. C. (1984) Nonenzymatic hydrolysis of RNA: Pb(II)-catalyzed site specific hydrolysis of tRNA. The role of the tertiary folding of the polynucleotide chain. Int J. Quant. Chem. 11, 355–366.

    Article  CAS  Google Scholar 

  38. Wrzesinski, J., Michalowski, D., Ciesiolka, J. and Krzyzosiak, W. J. (1995) Specific RNA cleavages induced by manganese ions. FEBS Lett. 374, 62–68.

    Article  PubMed  CAS  Google Scholar 

  39. Eckstein, F. and Lilley, D. M. (1996) Catalytic RNA, Springer, Berlin.

    Google Scholar 

  40. Hall, J., Hüsken, D. and Häner, R. (1996) Towards artificial ribonucleases: the sequence-specific cleavage of RNA in a duplex. Nucleic Acids Res. 24, 3522–3526.

    Article  PubMed  CAS  Google Scholar 

  41. Westheimer, F. H. (1968) Pseudo-rotation in the hydrolysis of phosphate esters. Acc. Chem. Res. 1, 70–78.

    Article  CAS  Google Scholar 

  42. Järvinen, P., Oivanen, M. and Lönnberg, H. (1991) Interconversion and phosphoester hydrolysis of 2′,5′- and 3′,5′-dinucleoside monophosphates: Kinetics and mechanism. J. Org. Chem. 56, 5396–5401.

    Article  Google Scholar 

  43. Kosonen, M., Oivanen, M. and Lönnberg, H. (1994) Hydrolysis and interconversion of the dimethyl esters of 5′-O-methyluridine 2′- and 3′-monophosphates: kinetics and mechanism, J. Org. Chem. 59, 3704–3708.

    Article  CAS  Google Scholar 

  44. Kosonen, M. and Lonnberg, H. (1995) General and specific acid/base catalysis of the hydrolysis and interconversion of ribonucleoside 2′- and 3′-phosphotriesters: kinetics and mechanisms of the reactions of 5′-O-pivaloyl 2′- and 3′-dimethylphosphates. J. Chem. Soc. Perkin Trans. 2, 1203–1209.

    Google Scholar 

  45. Kosonen, M., Hakala, K. and Lönnberg, H. (1998) Hydrolysis and intramolecular transesterification of ribonucleoside 3′-phosphotriesters: the effect of alkyl groups on the general and specific acid-base-catalyzed reactions of 5′-O-pivaloyluridin-3′-yl dialkyl phosphates. J. Chem. Soc. Perkin Trans. 2, 663–670.

    Google Scholar 

  46. Kosonen, M., Yousefi-Salakdeh, E., Strömberg, R., and Lönnberg, H. (1998) pH- and buffer-independent cleavage and mutual isomerization of uridine 2′-and 3′-alkyl phosphodiesters: implications for the buffer catalyzed cleavage of RNA. J. Chem. Soc. Perkin Trans. 2, 1589–1595.

    Google Scholar 

  47. Oivanen, M., Schnell, R., Pfleiderer, W. and Lönnberg, H. (1991) Interconversion and hydrolysis of monomethyl and monoisopropyl esters of adenosine 2′-and 3′-monophosphates: kinetics and mechanism. J. Org. Chem. 56, 3625–3628.

    Article  Google Scholar 

  48. Li, Y. and Breaker, R. R. (1999) Kinetics of RNA degradation by specific base catalysis of transesterification involving the 2′-hydroxyl group. J. Am. Chem. Soc. 121, 5364–5372.

    Article  CAS  Google Scholar 

  49. Kosonen, M., Yousefi-Salakdeh, E., Strömberg, R. and Lönnberg, H. (1997) Mutual isomerisation of uridine 2′-and 3′-alkylphosphates and cleavage to 2′,3′-cyclic phosphate: the effect of the alkyl group on the hydronium and hydroxide-ion-catalysed cleavage. J. Chem. Soc. Perkin Trans. 2, 2661–2666.

    Google Scholar 

  50. Dejaegere, A., Liang, X. and Karplus, M. (1994) Phosphate ester hydrolysis: Calculation of gasphase reaction paths and solvation effects. J. Chem. Soc. Faraday Trans. 90, 1763–1770.

    Article  CAS  Google Scholar 

  51. Anslyn, E. and Breslow, R. (1989) On the mechanism of catalysis by ribonuclease; cleavage and isomerizarion of the dinucleotide UpU catalysed by imidazole buffers. J. Am. Chem. Soc. 111, 4473–4482.

    Article  CAS  Google Scholar 

  52. Breslow, R., Dong, S. D., Webb, Y. and Xu, R. (1996) Further studies on the buffer-catalyzed cleavage and isomerization of uridylyluridine. Medium and ionic strentgh effects on catalysis by morpholine, imidazole and acetate buffers help clarify the mechanisms involved and their relationship to the mechanism used by the enzyme ribonuclease and by a ribonuclease mimic. J. Am. Chem. Soc. 118, 6588–6600.

    Article  CAS  Google Scholar 

  53. Beckmann, C., Kirby, A. J., Kuusela, S. and Tickle, D. C. (1998) Mechanism of catalysis by imidazole buffers of the hydrolysis and isomerisation of RNA models. J. Chem. Soc. Perkin Trans. 2., 573–581.

    Google Scholar 

  54. Menger, F. M. (1991) The negative rate constants of Breslow and Huang. J. Org. Chem. 56, 6251–6252.

    Article  CAS  Google Scholar 

  55. Haim, A. (1992) Imidazole buffer-catalyzed cleavage and isomerization reactions of dinucleotides: the proposed mechanism is incompatible with the kinetic measurements. J. Am. Chem. Soc. 114, 8384–8388.

    Article  CAS  Google Scholar 

  56. Perrin, C. L. (1995) On the mechanism of buffer-catalysed hydrolysis of RNA models. J. Org. Chem. 60, 1239–1243.

    Article  CAS  Google Scholar 

  57. Kuusela, S. and Lönnberg, H. (1992) Metal ion promoted hydrolysis of uridine 2′,3′-cyclic monophosphate of uridine. J. Phys. Org. Chem. 5, 803–811.

    Article  CAS  Google Scholar 

  58. Kuusela, S. and Lönnberg, H. (1993) Metal ions that promote the hydrolysis of nucleoside phosphoesters do not enhance intramolecular phosphate migration. J. Phys. Org. Chem. 6, 347–356.

    Article  CAS  Google Scholar 

  59. Kuusela, S., Rantanen, M. and Lönnberg, H. (1995) Metal-ion-promoted hydrolysis of uridylyl(3′,5′)uridine: internal vs. external genaral base catalysis. J. Chem. Soc. Perkin Trans. 2, 2269–2273.

    Google Scholar 

  60. Mikkola, S., Stenman, E., Nurmi, K., Yousefi-Salakdeh, E., Strömberg, R. and Lönnberg H. (1999) The mechanism of the metal ion promoted cleavage of RNA phosphodiester bonds involves a general acid catalysis by the metal aquo ion on the departure of the leaving group. J. Chem. Soc. Perkin Trans. 2, 1619–1625.

    Google Scholar 

  61. Komiyama, M., Matsumoto, Y., Takahashi, H., Shiiba, T., Tsuzuki, H., Yajima, H., Yashiro, M. and Sumaoka, J. (1998) RNA hydrolysis by cobalt(III) complexes. J. Chem. Soc. Perkin Trans. 2, 691–695.

    Google Scholar 

  62. Koike, T. and Kimura, E. (1991) Roles of zinc(II) ion in phosphatases. A model study with zinc(II)-macrocyclic polyamine complexes. J. Am. Chem. Soc. 113, 8935–8941.

    Article  CAS  Google Scholar 

  63. Oivanen, M., Mikhailov, S. N., Florentiev, V. L., Vihanto, P., and Lönnberg, H. (1993) Interconversion and hydrolysis of 1-[(2′S)-2′,3′-dihydroxypropyl]cytosine analogues of isomeric dinucleoside monophosphates, 2′,5′-CpA and 3′,5′-ApA. Acta Chem. Scand. 47, 622–625.

    CAS  Google Scholar 

  64. Holy, A. and Ivanova, G. S. (1974) Aliphatic analogs of nucleotides. Synthesis and affinity towards nucleases. Nucleic Acids Res. 1, 19–34.

    Article  PubMed  CAS  Google Scholar 

  65. Avramova, Z. V. and Dudkin, S. M. (1978) Role of the substrate ribose residues in reactions catalyzed by ribonucleases. Mol. Biol. (USSR) 12, 914–921.

    CAS  Google Scholar 

  66. Witzel, H. (1960) Einfluss der nucleotidbasen auf die nicht-enzymatische spaltung der ribonucleinsäure-diester bindungen. Liebigs Ann. Chem. 635, 182–191.

    Article  CAS  Google Scholar 

  67. Abrash, H. I., Cheung, C.-C. S. and Davis, J. C. (1967) The nonenzymic hydrolysis of nucleoside 2′,3′-phosphates. Biochemistry 6, 1298–1303.

    Article  CAS  Google Scholar 

  68. Oivanen, M. and Lönnberg, H. (1991) Hydrolysis and intramolecular transesterification of ribonucleoside phosphoesters. Trends Org. Chem. 2, 183–198.

    CAS  Google Scholar 

  69. Kuusela, S. and Lönnberg, H. (1994) Hydrolysis and isomerization of the internucleosidic phosphodiester bonds of polyuridylic acid: kinetics and mechanism. J. Chem. Soc. Perkin Trans. 2, 2109–2113.

    Google Scholar 

  70. Butzow, J. J. and Eichhorn, G. L. (1971) Interaction of metal ions with nucleic acids and related compounds. XVII. On the mechanism of degradation of polyribonucleotides and oligoribonucleotides by zinc(II) ions. Biochemistry 11, 2019–2027.

    Article  Google Scholar 

  71. Kuusela, S., Azhayev, A., Guzaev, A. and Lönnberg, H. (1995) The effect of the 3′-terminal monophosphate group on the metal-ion-promoted hydrolysis of the phosphodiester bonds of short oligonucleotides. J. Chem. Soc. Perkin Trans. 2, 1197–1202.

    Google Scholar 

  72. Kuusela, S. and Lönnberg, H. (1998) Catalytically significant macrochelate formation in Zn2+ promoted hydrolysis of oligoribonucleotides: model studies with chimeric phosphodiester/methylphosphonate oligomers. Nucleosides Nucleotides 17, 2417–2427.

    Article  CAS  Google Scholar 

  73. Kuusela, S. and Lönnberg, H. (1994) Metal-ion-promoted hydrolysis of polyuridylic acid. J. Chem. Soc. Perkin Trans 2, 2301–2306.

    Google Scholar 

  74. Kuusela, S. and Lönnberg, H. (1994) Zn2+ promoted hydrolysis of 3′,5′-dinucleoside monophosphates and polyribonucleotides. The effect of nearest neighbours on the cleavage of phosphodiester bonds. Nucleosides Nucleotides 15, 1669–1678.

    Article  Google Scholar 

  75. Ikenaga, H. and Inoue, Y. (1974) Metal(II) ion catalyzed transphosphorylation of four homodinucleotides and five pairs of dinucleotide sequence isomers. Biochemistry 13, 577–582.

    Article  PubMed  CAS  Google Scholar 

  76. Kuusela, S., Guzaev, A. and Lönnberg, H. (1996) Acceleration of the Zn2+ promoted phosphodiester hydrolysis of oligonucleotides by the 3′-terminal monophosphate group: intrastrand participation over several nucleoside units. J. Chem. Soc. Perkin Trans. 2, 1895–1899.

    Google Scholar 

  77. Breslow, R. and Huang, D.-L. (1991) Effects of metal ions, including Mg2+ and lanthanides, on the cleavage of ribonucleotides and RNA model compounds. Proc. Natl. Acad. Sci. USA 88, 4080–4083.

    Article  PubMed  CAS  Google Scholar 

  78. Morrow, J. R., Buttrey, L. A. and Berback, K. A. (1992) Transesterification of a phosphate diester by divalent and trivalent metal ions. Inorg. Chem. 31, 16–20.

    Article  CAS  Google Scholar 

  79. Saenger, W. (1984) The Structure of Nucleic Acids, Springer, Berlin.

    Google Scholar 

  80. Usher, D. A. and McHale, A. H. (1976) Hydrolytic stability of helical RNA; a selective advantage for the natural 3′,5′-bond. Proc. Natl. Acad. Sci. USA 73, 1149–1153.

    Article  PubMed  CAS  Google Scholar 

  81. Zaug, A. J. and Cech, T. R. (1986) The intervening sequence RNA of Tetrahymena is an enzyme. Science 231, 470–475.

    Article  PubMed  CAS  Google Scholar 

  82. Vlassov, V. V., Zuber, G., Felden, B., Behr, J.-P., and Giege, R. (1995) Cleavage of tRNA with imidazole constructs: a new approach for probing RNA structure. Nucleic Acids Res. 23, 3161–3167.

    Article  PubMed  CAS  Google Scholar 

  83. Reynolds, M. A., Beck, T. A., Say, P. B., Schwartz, D. A., Dwyer, B. P., Daily, W. J., Vaghefi, M. M., Metzler, M. D., Klem, R. E., and Arnold, L. J., Jr. (1996) Antisense oligonucleotides containing an internal non-nucleotide-based linker promote site-specific cleavage of RNA. Nucleic Acids Res. 24, 760–765.

    Article  PubMed  CAS  Google Scholar 

  84. Hayashi, N., Takeda, N., Shiiba, T., Yashiro, M., Watanabe, K. and Komiyama, M. (1993) Site-selective hydrolysis of tRNA by lanthanide metal complexes. Inorg. Chem. 32, 5899–5900.

    Article  CAS  Google Scholar 

  85. Soukup, G. A. and Breaker, R. R. (1999) Relationship between internucleosidic linkage geometry and the stability of RNA. RNA 5, 1308–1325.

    Article  PubMed  CAS  Google Scholar 

  86. Laing, L. G. and Hall, K. B. (1996) A model of the iron responsive element RNA hairpin loop structure determined from NMR and thermodynamic data. Biochemistry 35, 13,586–13,596.

    Article  CAS  Google Scholar 

  87. Molinaro, M. and Tinoco, I., Jr. (1995) Use of ultra stable UNCG tetraloop hairpins to fold RNA structures: thermodynamics and spectroscopic applications. Nucleic Acids Res. 23, 3056–3063.

    Article  PubMed  CAS  Google Scholar 

  88. Portmann, S., Grimm, S., Workman, C., Usman, N., and Egli, M. (1996) Crystal structures of an A-form duplex with single-adenosine bulges and a conformational basis for site-specific RNA self-cleavage. Chem. Biol. 3, 173–184.

    Article  PubMed  CAS  Google Scholar 

  89. Endo, M., Hirata, K., Ihara, T., Sueda, S. S., Takagi, M., and Komiyama, M. (1996) RNA hydrolysis by the cooperation of the carboxylate ion and ammonium ion. J. Am. Chem. Soc. 118, 5478–5479.

    Article  CAS  Google Scholar 

  90. Podymigonin, M. A., Vlassov, V. V., and Giege, R. (1993) Synthetic RNA-cleaving molecules mimicking ribonuclease A active center. Design and cleavage of tRNA transcripts. Nucleic Acids Res. 21, 5950–5956.

    Article  Google Scholar 

  91. Keck, M. V. and Hecht, S. M. (1995), Sequence-specific hydrolysis of yeast tRNAPhe mediated by metal-free bleomycin. Biochemistry 34, 12,029–12,037.

    Article  CAS  Google Scholar 

  92. Sreedhara, A., Patwardhan, A., and Cowan, A. A. (1999) Novel reagents for targeted cleavage of RNA sequences: towards a new family of inorganic pharmaceuticals. Chem. Commun., 1147–1148.

  93. Hegg, E. L., Deal, K. A., Kiessling, L. L., and Burstyn, J. N. (1997) Hydrolysis of double-stranded and single-stranded RNA in hairpin structures by the copper(II) macrocycle Cu([9]aneN3)Cl2 Inorg. Chem. 36, 1715–1718.

    Article  PubMed  CAS  Google Scholar 

  94. Kierzek, R. (1992). Hydrolysis of oligoribonucleotides: Influence of sequence and length. Nucleic Acids Res. 20, 5073–5077.

    Article  PubMed  CAS  Google Scholar 

  95. Hosaka, H., Sakabe, I., Sakamoto, K., Yokoyama, S., and Takaku, H. (1994) Sequence-specific cleavage of oligoribonucleotide capable of forming a stem and loop structure. J. Biol. Chem. 269, 20,090–20,094.

    CAS  Google Scholar 

  96. Ciesiolka, J., Lorenz, S., and Erdmann, V. A. (1992) Different conformational forms of Escherichia coli and rat liver 5SrRNA revealed by Pb(II)-induced hydrolysis. Eur. J. Biochem. 204, 583–589.

    Article  CAS  Google Scholar 

  97. Lane, B. G. and Butler, G. C. (1959) The exceptional resistance of certain oligoribonucleotides to alkaline degradation. Biochim. Biophys. Acta 33, 281–283.

    Article  PubMed  CAS  Google Scholar 

  98. Smith, K. C. and Allen, F. W. (1953) The liberation of polynucleotides by the alkaline hydrolysis of ribonucleic acid from yeast. J. Am. Chem. Soc. 75, 2131–2133.

    Article  CAS  Google Scholar 

  99. Norberg, J. and Nilsson, L. (1995) Stacking free energy profiles for all 16 natural ribodinucleoside monophosphates in aqueous solution. J. Am. Chem. Soc. 117, 10,832–10,840.

    Article  CAS  Google Scholar 

  100. Ciesiolka, J., Michalowski, D., Wrzesinski, J., Krajewski, J., and Krzyzosiak, W. J. (1998) Patterns of cleavage induced by lead ions in defined RNA secondary structure motifs. J. Mol. Biol. 275, 211–220.

    Article  PubMed  CAS  Google Scholar 

  101. Ciesiolka, J., Gorski, Y., and Yarus, M. (1995) Selection of an RNA domain that binds Zn2+. RNA 1, 538–550.

    PubMed  CAS  Google Scholar 

  102. Ciesiolka, J. and Krzyzosiak, W. J. (1996) Structural analysis of two plant 5S rRNA species and fragments thereof by lead-induced hydrolysis. Biochem. Mol. Biol. Int. 39, 319–328.

    PubMed  CAS  Google Scholar 

  103. Ciesiolka, J., Lorenz, S., and Erdmann, V. A. (1992) Structural analysis of three prokaryotic 5S rRNA species and selected 5S rRNA-ribosomal-protein complexes by means of Pb(II)-induced hydrolysis. Eur. J. Biochem. 204, 575–581.

    Article  PubMed  CAS  Google Scholar 

  104. Cheong, Ch., Varani, G., and Tinoco, I., Jr. (1990) Solution structure of an unusually stable RNA hairpin, 5′-GGAC(UUCG)GUCC. Nature 346, 680–682.

    Article  PubMed  CAS  Google Scholar 

  105. Heus, H. A. and Pardi, A. (1991) Structural features that give rise to the unusual stability of RNA hairpins containing GNRA loops. Science 253, 191–194.

    Article  PubMed  CAS  Google Scholar 

  106. Farkas, W. R. (1968) Depolymerisation of ribonucleic acid by plumbous ion. Biochim. Biophys. Acta 155, 401–409.

    PubMed  CAS  Google Scholar 

  107. Brown, R. S., Hingerty, B. E., Dewan, J. C., and Klug, A. (1983) Pb(II)-catalysed cleavage of the sugar-phosphate backbone of yeast tRNAPhe—implications for lead toxicity and self-splicing RNA. Nature 303, 543–546.

    Article  PubMed  CAS  Google Scholar 

  108. Michalowski, D., Wrzesinski, J., Ciesiolka, J., and Krzyzosiak, W. J. (1996) Effect of modified nucleotides on structure of yeast thRNAPhe. Comparative studies by metal ion-induced hydrolysis and nuclease mapping. Biochimie 78, 131–138.

    Article  PubMed  CAS  Google Scholar 

  109. Michalowski, D., Wrzesinski, J., and Krzyzosiak, W. J. (1996) Cleavages induced by different metal ions in Yeast tRNAPhe U59C60 mutants. Biochemistry 35, 10,727–10,734.

    Article  CAS  Google Scholar 

  110. Behlen, L. S., Sampson, J. R., DiRenzo, A. B., and Uhlenbeck, O. C. (1990) Lead-catalysed cleavage of yeast tRNAPhe mutants. Biochemistry 29, 2515–2523.

    Article  PubMed  CAS  Google Scholar 

  111. Rordorf, B. T. and Kearns, D. R. (1976) Effect of europium(III) on the thermal denaturation and cleavage of transfer ribonucleic acids. Biopolymers 15, 1491–1504.

    Article  PubMed  CAS  Google Scholar 

  112. Ciesiolka, J., Marciniec, T., and Krzyzosiak, W. J. (1989) Probing the environment of lanthanide binding sites in yeast tRNAPhe by specific metal-ion-promoted cleavages. Eur. J. Biochem. 182, 445–450.

    Article  PubMed  CAS  Google Scholar 

  113. Pan, T. and Uhlenbeck, O. C. (1992) In vitro selection of RNA’s that undergo autolytic cleavage in the presence of Pb2+. Biochemistry 31, 3887–3895.

    Article  PubMed  CAS  Google Scholar 

  114. Pan, T. and Uhlenbeck, O. C. (1992) A small metalloribozyme with a two-step mechanism. Nature 358, 560–563.

    Article  PubMed  CAS  Google Scholar 

  115. Ohmichi, T. and Sugimoto, N. (1997) Role of Nd3+ and Pb2+ on the RNA cleavage reaction by a small ribozyme. Biochemistry 36, 3514–3521.

    Article  PubMed  CAS  Google Scholar 

  116. Pan, T., Dichtl, B., and Uhlenbeck, O. C. (1994) Properties of an in vitro selected Pb2+ cleavage motif. Biochemistry 33, 9561–9565.

    Article  PubMed  CAS  Google Scholar 

  117. Chartrand, P., Usman, N., and Cedergren, R. (1997) Effect of structural modifications on the activity of the leadzyme. Biochemistry 36, 3145–3150.

    Article  PubMed  CAS  Google Scholar 

  118. Wedekind, J. E. and McKay, D. B. (1999) Crystal structure of a lead-dependent ribozyme revealing metal binding sites relevant to catalysis. Nature Struct. Biol. 6, 261–268.

    Article  PubMed  CAS  Google Scholar 

  119. Hoogstraten, C. G., Legault, P., and Pardi, A. (1998) NMR solution structure of the lead-dependent ribosyme: evidence for dynamics in RNA catalysis. J. Mol. Biol. 284, 337–350.

    Article  PubMed  CAS  Google Scholar 

  120. Legault, P., Hoogstraten, C. G., Metlitzky, E., and Pardi, A. (1998) Order, dynamics and metal-binding in the lead-dependent ribozyme. J. Mol. Biol. 284, 325–335.

    Article  PubMed  CAS  Google Scholar 

  121. Dange, V., Van Atta, R. B., and Hecht, S. M. (1990) A Mn2+ dependent ribozyme. Science 248, 585–588.

    Article  PubMed  CAS  Google Scholar 

  122. Kazakov, S. and Altman, S. (1992) A trinucleotide can promote metal ion-dependent specific cleavage of RNA. Proc. Natl. Acad. Sci. USA 89, 7939–7943.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mikkola, S., Kaukinen, U. & Lönnberg, H. The effect of secondary structure on cleavage of the phosphodiester bonds of RNA. Cell Biochem Biophys 34, 95–119 (2001). https://doi.org/10.1385/CBB:34:1:95

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/CBB:34:1:95

Keywords

Navigation