Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Review
  • Published:

From housekeeper to microsurgeon: The diagnostic and therapeutic potential of ribonucleases

Nature Biotechnology volume 15, pages 529–536 (1997)Cite this article

Abstract

The RNA population in cells is controlled post-transcriptionally by ribonucleases (RNases) of varying specificity. Angiogenin, neurotoxins, and plant allergens are among many proteins with RNase activity or significant homology to known RNases. RNase activity in serum and cell extracts is elevated in a variety of cancers and infectious diseases. RNases are regulated by specific activators and inhibitors, including interferons. Many of these regulatory molecules are useful lead compounds for the design of drugs to control tumor angiogenesis, allergic reactions, and viral replication. One RNase (Onconase) and several RNase activators are now in clinical trials for cancer treatment or inhibition of chronic virus infections. Several others, alone or conjugated with specific cell binding molecules, are being developed for their antifungal, antiviral, and antitumor cell activity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Confalone, E., Bemtema, J.J., Sasso, M.P., Carsana, A., Palmien, M., Vento, M.T., and Funa, A. 1995. Molecular evolution of genes encoding ribonucleases in ruminant species. J. Mol. Evol. 41: 850–858.

    CAS  PubMed  Google Scholar 

  2. Tharun, S. and Sirdeshmukh, R. 1995. Specific endonucleolytic cleavages of mouse albumin mRNA and their modulation during liver development. Nuc Acids Res. 23: 641–6.

    CAS  Google Scholar 

  3. Rosenberg, H.F. and Dyer, K.D. 1995. Human nbonuclease 4 (RNase 4) coding sequence, chromosomal localization and identification of two distinct transcripts in human somatic tissues Nuc Acids Res. 23: 4290–4295.

    CAS  Google Scholar 

  4. Reddi, K.K. 1975. Nature and possible origin of human serum ribonuclease. Biochem. & Biophys. Res. Comm. 67: 110–118.

    CAS  Google Scholar 

  5. Bartholeyns, J.A.U., Peeters-Jons, C.A.U., and Baudhum, P. 1975. Hepatic nucleases Extrahepatic origin and association of neutral liver nbonuclease with lysosomes. Eur. J. Biochem. 60: 385–393.

    CAS  PubMed  Google Scholar 

  6. Liu, D.K. and Owens, G.F. 1983. Mammary origin of rat milk nbonuclease. Inter J Biochem. 15: 1273–1277.

    CAS  Google Scholar 

  7. Weickmann, J.L. and Glitz, D.G. 1982. Human nbonucleases Quantitation of pancreatic-like enzymes in serum, urine, and organ preparations. J. Biol. Chem. 257: 8705–8710.

    CAS  PubMed  Google Scholar 

  8. Menella, M.R. and Jones, M.R. 1977. The activity of some nucleolytic enzymes in semen and in the secretion of the male reproductive tract. Andrologia. 9: 15–22.

    Google Scholar 

  9. Tiffany, H.L., Handen, J.S., and Rosenberg, H.F. 1996.Enhanced expression of the eosmophil-derived neurotoxin nbonuclease (RNS2) gene requires interaction between the promoter and the mtron. J. Biol. Chem. 271: 12387–12393.

    CAS  PubMed  Google Scholar 

  10. Chow, J. and Dennis, P.P. 1994. Coupling between mRNA synthesis and mRNA stability in Eschenchia coli. Mol. Microbiol. 11: 919–931.

    CAS  PubMed  Google Scholar 

  11. Jam, C. and Belasco, J.G., RNase, E.G. 1995. RNase E autoregulates its synthesis by controlling the degradation rate of its own mRNA in Eschenchia coliunusual sensitivity of the rne transcript to RNase E activity. Genes & Devel. 9: 84–96.

    Google Scholar 

  12. Presutti, C., Villa, T.A.U., Hall, D., Pertica, C., and Bozzoni, I. 1995. Identification of the cis-elements mediating the autogenous control of ribosomal protein L2 mRNA stability in yeast EMBOJ. 14: 4022–4030.

    CAS  Google Scholar 

  13. Dementiev, A.A., Mirgorodskaya, O.A., Moiseyev, G.P., Yakovlev, G.I., Shlyapnikov, S.V., and Kirpichnikov, M.P. 1996. A novel guanyl-preferable nbonuclease ofBacilluspolymyxa-isolation and characterization of the enzyme. Biochem. & Mol. Biol. Intl. 39: 159–170.

    CAS  Google Scholar 

  14. Kobe, B. and Deisenhofer, J. 1995. A structural basis of the interactions between leucme rich repeats and protein ligands. Nature. 374: 183–186.

    CAS  PubMed  Google Scholar 

  15. Hofsteenge, J. 1994. ‘Holy’ proteins I Ribonuclease inhibitor. Curr. Opin. Struct. Biol. 4: 807–809.

    CAS  PubMed  Google Scholar 

  16. Schneider, R. and Schweiger, M. 1992. The yeast RNA1 protein, necessary for RNA processing, is homologous to the human nbonuclease/angiogenm inhibitor (RAI). Mol. Gen. Genet. 233: 315–318.

    CAS  PubMed  Google Scholar 

  17. Nadano, D., Yasuda, T., Takeshita, H., Uchide, K., and Kishi, K. 1994. Purification and characterization of human brain nbonuclease inhibitor. Archives Biochem. Biophy. 312: 421–428.

    CAS  Google Scholar 

  18. Stoeckle, M.Y. and Guan, L. 1993. High-resolution analysis of groa mRNA poly(A) shortening regulation by mterleukm-1β. Nuc Acids. Res. 21: 1613–1617.

    CAS  Google Scholar 

  19. Lengyel, P. 1993. Tumor-suppressor genes news about the interferon connection. Proc Natl. Acad. Sci. 90: 5893–5895.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Cole, J.L., Carroll, S.S., and Kuo, L.C. 1996. Stoichiometry of 2′5′ohgoadenylate induced dimenzation of nbonuclease L—a sedimentation equilibrium study. J. Biol. Chem. 271: 3979–3981.

    CAS  PubMed  Google Scholar 

  21. Bisbal, C., Martmand, C., Silhol, M., Lebleu, B., and Salehzada, T. 1995. Cloning and characterization of a RNase L inhibitor A new component of the iterferon-regulated 2–5A pathway. J. Biol. Chem. 270: 13308–13317.

    CAS  PubMed  Google Scholar 

  22. Schem, C.H., Haugg, M., and Benner, S.A. 1990. Interferon-γ activates the cleavage of double stranded RNA by bovine seminal ribonuclease. FEBS Letters 270: 229–232.

    Google Scholar 

  23. Schem, C.H. and Haugg, M. 1995. The role of the C-termmus of human interferon-γ in RNA binding and activation of the cleavage of ds RNA by bovine seminal nbonuclease. Biochem. J. 307: 123–127.

    Google Scholar 

  24. Gessani, S., DiMarzio, P., Rizza, P., Belardelh, F., and Baglioni, C. 1991. Post-transcriptional regulation of interferon mRNA levels in peritoneal macrophages. J. Virol. 65: 989–991.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Lappm, D.F., Guc, D., Hill, A., McShane, T., and Whaley, K. 1992. Effect of interferon-γ on complement gene expression in different cell types. Biochem. J. 281: 437–442.

    Google Scholar 

  26. Radzich, D. and Varesio, L. 1991. c-fos mRNA expression in macrophages is downregulated by interferon-γ at the post-transcnptional level. Mol. Cell. Biol. 11: 2718–2722.

    Google Scholar 

  27. Kasama, T., Stricter, R.M., Lukacs, N.W., Lincoln, P.M., Burdick, M.D., and Kunkel, S.L. 1995. Interferon gamma modulates the expression of neutrophil-derived chemokmes. J. Invest. Mad. 43: 58–67.

    CAS  Google Scholar 

  28. Besancon, F., Przewlocki, G., Baro, I., Hongre, A., Escande, D.,and Edelman, A. 1994. Interferon-γ downregulates CFTR expression in epithelial cells. Am. J. Physiol. (Cel Physiol) 36: C1398–C1404.

    Google Scholar 

  29. Schem, C.H. 1997. An enzymatic cell free assay to detect direct inhibitors of interferon-γ. In. Vitro Toxicol. In press.

    Google Scholar 

  30. Albanese, A.A., Lorenze, E.J., Orto, L.A., Wem, E.A., Zavattoro, D.M., and Carlo, R.D. 1972. Nutritional and metabolic effects of some newer steroids VI Serum Ribonuclease. N. Y. State J. Med. 19: 1595–1600.

    Google Scholar 

  31. Menella, M.R. and Jones, M.R. 1977. The activity of some nucleolytic enzymes in semen and in the secretion of the male reproductive tract. Andrologia 9: 15–22.

    Google Scholar 

  32. Zelenko, O., Neumann, U., Brill, W., Pieles, U., Moser, H. E., and Hofsteenge, J. 1994. A novel fluorogenic substrate for nbonucleases Synthesis and enzymatic characterization. Nucl. Acids. Res. 22: 2731–2739.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Newton, D. L., Walbridge, S., Mikulski, S. M., Ardelt, W., Shogen, K., Ackerman, et al. 1994. Toxicity of an antitumor nbonuclease to Purkmje neurons. J. Neuroscience. 14: 538–544.

    CAS  Google Scholar 

  34. Bufe, A., Spangfort, M.D., Kahlert, H., Schlaak, M., and Becker, W.M. 1996. The major birch pollen allergen, BEt V1, shows ribonuclease activity. Planta. 199: 413–415.

    CAS  PubMed  Google Scholar 

  35. Sassa, H., Nishio, T., Kowyama, Y., Hirano, H., Koba, T., and Ikehashi, H., 1996. Self incompatibility (S) alleles of the Rosaceaeencode members of a distinct class of the T2/S ribonuclease superfamily. Mol. & Gen. Genet. 250: 547–557.

    CAS  Google Scholar 

  36. Ye, Z.H. and Droste, D.L. 1996. Isolation and characterization of cDNAs encoding Xylogenesis-associated and wound-inducing nbonucleases in Zinnia elegans. Plant Mol. Biol. 30: 697–709.

    CAS  PubMed  Google Scholar 

  37. Walter, M.H., Liu, J.W., Wunn, J., and Hess, D. 1996. Bean nbonuclease-like pathogenesis related protein genes (YPR10) display complex patterns of developmental, dark induced and exogenous-stimulus-dependent expression. Eur. J. Biochem. 239: 281–293.

    CAS  PubMed  Google Scholar 

  38. Francesconi, M., Meryn, S., Rogan, A.M., Szalay, S., Graninger, W., and Schmidbauer, C.P. 1984. Poly (C) avid ribonuclease estimation in patients with solid tumors A critical evaluation. Cancer. 53: 1927–1930.

    CAS  PubMed  Google Scholar 

  39. Hatzelmann, A., Tenor, H., and Schudt, C. 1995. Differential effects of non-selective and selective phosphodiesterase inhibitors on human eosmophil functions. British J. Pharmacol. 114: 821–831.

    CAS  Google Scholar 

  40. Okada, N. and Koizumi, S. 1995. A neuroprotective compound, aurm tricarboxylic acid, stimulates the tyrosme phosphorylation cascade in PC12 cells. J. Biol. Chem. 270: 16464–16469.

    CAS  PubMed  Google Scholar 

  41. Murphy, N.R., Lembach, S.S., and Hellwig, R.J. 1995. A potent, cost-effective RNase inhibitor BioTechmques. 18: 1068–1073.

    CAS  Google Scholar 

  42. Ogawa, T., Hori, T., and Ishida, I. 1996. Virus-induced cell death in plants expressing the mammalian 2′,5′ oligoadenylate system. Nature Biotechnology. 14: 1566–1569.

    CAS  PubMed  Google Scholar 

  43. Sobol, R.W., Henderson, E.E., Kon, N., Shao, J., Hitzges, P., Mordechai, E., Reichenbach, N.L., Charubala, R., Schirmeister, H., Pfleiderer, W., and Suhadolmk, R.J. 1995. Inhibition of HIV-1 replication and activation of RNase L by phosphorothioate/phosphodiester 2′,5′-ohgoadenylate derivatives. J. Biol. Chem. 270: 5963–5978.

    CAS  PubMed  Google Scholar 

  44. Fmgerote, R.J., Cruz, B.M., Gorczynski, R.M., Fung, L.S., Hubbell, H.R., Suhadolnik, R.J., and Levy, G.A., 1995. A 2′,5′-ohgoadenylate analogue inhibits munne hepatitis virus strain 3 (MHV-3) replication in vitro but does not reduce MHV-3-related mortality or induction of procoagulant activity in susceptible mice. J. Gen. Virol. 76: 373–380.

    Google Scholar 

  45. Ushijima, H., Rytik, P.G., Schacke, H., Scheffer, U., Muller, W.E., and Schroder, H.C. 1993. Mode of action of the anti-AIDS compound poly(l) poly(C12U) (Amphgen) activator of 2′,5′-ohgoadenylate synthetase and double-stranded RNA-dependent kmase. J. Interferon Res. 13: 161–171.

    CAS  PubMed  Google Scholar 

  46. Cheney, P., Salvato, P., Thompson, C., Loveless, M., Muller, W.E. et al. 1994. Changes in the 2—5A synthetase/RNase L antiviral pathway in a controlled clinical trial with poly(l)-poly(C12U) in chronic fatigue syndrome. In Vivo. 8: 599–604.

    PubMed  Google Scholar 

  47. Liao, Y.D., Huang, H.C., Chan, H.J., and Kuo, S.J. 1996. Large-scale preparation of a ribonuclease from flana catesbeiana(bullfrog) oocytes and characterization of its specific cytotoxic activity against tumor cells. Prof. Express. Punf. 7: 194–202.

    CAS  Google Scholar 

  48. Rybak, S.M., Pearson, J.W., Fogler, W.E., Volker, K., Spence, S.E., Newton, D.L., Mikulski, S.M., Ardelt, W., Riggs, C.W., Kung, H.F., and Longo, D.L. 1996. Enhancement of vincnstme cytotoxicity in drug-resistant cells by simul taneous treatment with onconase, an antitumor ribonuclease. J. Natl. Cancer Inst. 88: 747–753.

    CAS  PubMed  Google Scholar 

  49. Newton, D.L., Pearson, J.W., Xue, Y., Smith, M.R., Fogler, W.E., Mikulski, S.M., Alvord, W.G., Kung, H.F., Longo, D.L., and Rybak, S.M. 1996. Anti-tumor ribonuclease, combined with or conjugated to monclonal antibody MRK16, overcomes multidrug resistance to vincnstme in vitro and in vivo. Int. J. Oncol. 8: 1095–1104.

    CAS  PubMed  Google Scholar 

  50. Haugg, M. and Schem, C.H. 1992. The DNA sequences of the human and hamster secretory nbonucleases determined with the polymerase chain reaction (PCR). Nuc. Acids. Res. 20: 612.

    CAS  Google Scholar 

  51. Rosenberg, H.F. and Dyer, K.D. 1995. Eosmophil cationic protein and Eosmophil neurotoxin Evolution of novel function in a primate ribonuclease gene family. J. Biol. Chem. 270: 21539–21544.

    CAS  PubMed  Google Scholar 

  52. Dong, B., Xu, L., Zhou, A., Hassel, B.A., Lee, X., Torrence, P.F., and Silverman, R.H. 1994. Intrinsic molecular activities of the mterferon-mduced 2—5A-dependentRNA. J. Biol. Chem. 269: 14153–14158.

    CAS  PubMed  Google Scholar 

  53. Wennborg, A., Sohlberg, B., Angerer, D., Klein, G., and Von Gobain, A., 1995. A human RNase E-hke activity that cleaves RNA sequences involved in mRNA stability control. Proc. Natf. Acad. Sci. 92: 7322–7326.

    CAS  Google Scholar 

  54. Boeck, R., Tarun, S., Rieger, M., Deardorff, J.A., Muller-Auer, S., and Sachs, A.B. 1996. The yeast PAN2 protein is required for poly (A) binding-protein stimulated poly (A) nuclease activity J. Biol. Chem. 271: 432–438.

    CAS  PubMed  Google Scholar 

  55. Trabesmgerruef, N., Jermann, T., Zankel, T., Durrant, B., Frank, G., and Benner, S.A. 1996. Pseudogenes in ribonuclease evolution—a source of new blomacromolecular function. FEBS Letters. 382: 319–322.

    Google Scholar 

  56. Boix, E., Nogués, M.V., Schem, C.H., Benner, S.A., and Cuchillo, C.M. 1994. Reverse transphosphorylation by ribonuclease A needs an intact p2 binding site Point mutations at Lys 7 and Arg-10 alter the catalytic properties of the enzyme. J. Biol. Chem. 269: 2529–2534.

    CAS  PubMed  Google Scholar 

  57. Moussaoui, M., Guasch, A., Boix, E., Cuchillo, C.M., and Nogués, M.V. 1996. The role of non-catalytic binding subsites in the endonuclease activity of bovine pancreatic ribonuclease A. J. Biol. Chem. 271: 4687–4692.

    CAS  PubMed  Google Scholar 

  58. Mosimann, S.C., Ardelt, W., and James, M.N.G. 1994. 1.7 Å X-ray crystalographic structure of P-30 protein, an amphibian ribonuclease with antitumor activity. J. Mol. Biol. 236: 1141–1153.

    CAS  PubMed  Google Scholar 

  59. Mosimann, S.C., Newton, D.L., Youle, R.J., and James, M.N.G. 1996. X-ray crystallographic structure of recombmant eosmophil-denved neurotoxm at 1.83 Å resolution. J. Mol. Biol. 260: 540–552.

    CAS  PubMed  Google Scholar 

  60. Lequm, O., AJbaret, C., Bontems, F., Spik, G., and Lallemand, J.Y. 1996. Solution structure of bovine angiogenm by H-1 nuclear magnetic resonance spectroscopy. Biochem. 35: 8870–8880.

    Google Scholar 

  61. Kim, J.S., Soucek, J., Matousek, J., and Raines, R.T. 1995. Mechanism of nbonuclease cytotoxicity. J. Biol. Chem. 270: 31097–31102.

    CAS  PubMed  Google Scholar 

  62. Capasso, S., Didonato, A., Esposito, L., Sica, R., Sorrentino, G., Vitagliano, L. et al. 1996. Deamidation in proteins—the crystal structure of bovine pancreatic rlbonuclease with an isoaspartyl residue at position 67. J. Mol. Biol. 257: 492–496.

    CAS  PubMed  Google Scholar 

  63. Boix, E., Wu, Y.N., Vasandani, V.M., Saxena, S.K., Ardelt, W., Ladner, J., and Youle, R.J. 1996. Role of the N terminus in RNase A Homologues— Differences in catalytic activity, rlbonuclease inhibitor interaction and cytotoxicity. J. Mol. Btol. 257: 992–1007.

    CAS  Google Scholar 

  64. Carroll, S.S., Ghen, E., Viscount, T., Geib, J., Sardana, M.K., Gehman, J., and Kuo, L.C. 1996. Cleavage of oligoribonucleotides by the 2′5′-oligoadenylate-dependent nbonuclease L. J. Biol. Chem. 271: 4988–4992.

    CAS  PubMed  Google Scholar 

  65. Okorokov, A.L., Panov, K.I., Kolbanovskaya, E.Y., Karpeisky, M.Y., Polyakov, K.M., Wilkmson, A.J., and Dodson, G.G. 1996. Site-directed mutagenesis of the base recognition loop of nbonuclease from Bacillus intermedius (bmase) . FEBS Letters. 384: 143–146.

    CAS  PubMed  Google Scholar 

  66. Parente, D., Raucci, G., Celano, B., Pacilli, A., Zanoni, L., Canevan, S. et al. 1996. Clavm A Type-1 nbosome-inactivating protein from Aspergillus clavatus IFO 8605-cDNA isolation, heterologous expression, biochemical and biological characterization for the recombmant protein. Eur. J. Biochem. 239: 272–280.

    CAS  PubMed  Google Scholar 

  67. Szewczak, A.A., Moore, P.B., Chang, Y.L., and Wool, I.G. 1993. The conformation of the Sarcri/ricin loop from 28S nbosomal RNA. Proc. Natl. Acad. Sci. 90: 9581–9585.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Wool, I.G. 1984. The mechanism of action of the cytotoxic nuclease α-sarcin and its use to analyse nbosome structure. TIBS. 9: 14–17.

    CAS  Google Scholar 

  69. Cheung, J.I., Wang, Y.R., and Lm, A. 1996. Substrate specificity of monomeric and dimenc alpha-sarcm FEBS Letters. 386: 60–64.

    CAS  PubMed  Google Scholar 

  70. Morris, K.N. and Wool, I.G. 1992. Determination by systematic deletion of the ammo acids essential for catalysis by ricin A chain. Proc. Natl. Acad Sci. 89: 4869–4873.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Py, B., Causton, H., Mudd, E.A., Higgms, C.F. 1994. A protein complex mediating mRNA degradation in Eschenchia coll . Mol. Microbiol. 14: 717–729.

    CAS  PubMed  Google Scholar 

  72. Carpousis, A.J., Van Houwe, G., Ehretsmann, C., and Knsch, H.M. 1994. Copunfication of E. coliRNAase E and PNPase: evidence for a specific association between two enzymes important in RNA processing and degradation. Cell. 76: 889–900.

    CAS  PubMed  Google Scholar 

  73. Cazenave, C., Frank, P., Toulme, J.J., and Busen, W. 1994. Characterization and subcellular localization of nbonuclease H activities from Xenopus laevis oocytes . J. Biol. Chem. 269: 25185–15192.

    CAS  PubMed  Google Scholar 

  74. Hue, K.K., Cohen, S.D., and Bechhofer, D.H. 1995. A polypunne sequence that acts as a 5′ mRNA stabilizer in Bacillus subtilis .J. Bactenol. 177: 3465–3471.

    CAS  Google Scholar 

  75. Kowalak, J.A., Dalluge, J.J., McCloskey, J.A., and Stetter, K.O. 1994. The role of posttranscnptional modification in stabilization of transfer RNA from hyperthermophiles. Biochem. 33: 7869–7876.

    CAS  Google Scholar 

  76. Kowalak, J.A., Pomerantz, S.C., Cram, P.F., and McCloskey, J.A. 1993 A novel method for the determination of post-transcnptional modification in RNA by mass spectrometry. Nuc. Acids Res. 21: 4577–4585.

    CAS  Google Scholar 

  77. Giles, R.V., Spiller, D.G., and Tidd, D.M. 1995. Detection of rlbonuclease H-generated mRNA fragments in human leukemia cells following reversible membrane permeabillzation in the presence of antisense oligodeoxynucleotides. Antisense Res. & Devel. 5: 23–31.

    CAS  Google Scholar 

  78. Augustyns, K., Godard, G., Hendnx, C., Van Aerschot, A., Rozenski, J., Saison-Behmoaras, T., and Herdewijn, P. 1993. Hybridization specificity, enzymatic activity and biological(Ha-ras) activity of oligonucleotides containing 2,4-dideoxy-beta-D-erythro-hexopyranosyl nucleosides. Nuc. Acids. Res. 21: 4670–4676.

    CAS  Google Scholar 

  79. Giles, R.V., Ruddell, C.J., Spiller, D.G., Green, J.A., and Tidd, D.M. 1995. Single base discrimination for rlbonuclease H-dependent antisense effects within intact human leukaemia cells. Nuc. Acids. Res. 23: 954–961.

    CAS  Google Scholar 

  80. Blam, S.W., Hendrickson, W.A., and Goff, S.P. 1995. Reversion of a Moloney munne leukemia virus RNase H mutant at a second site restores enzyme function and mfectivity. J. Virol. 69: 5113–5116.

    Google Scholar 

  81. Blam, S.W. and Goff, S.P. 1993. Nuclease activities of Moloney munne leukemia virus reverse transcnptase. Mutants with altered substrate specificities. J. Biol. Chem. 268: 23585–23592. The authors used a gel based solid state assay to eliminate the possibility that the proteins were contaminated with E. coliRNase III.

    Google Scholar 

  82. Gbtte, M., Fackler, S., Hermann, T., Perola, E., Cellai, L., Gross, H.J., et al. 1995. HIV-1 reverse transcnptase-associated RNase H cleaves RNA/RNA in arrested complexes, implications for the mechanism by which RNase H discriminates between RNA/RNA and RNA/DNA. EMBOJ. 14: 833–841.

    Google Scholar 

  83. Palaniappan, C., Fay, P.J., and Bambara, R.A. 1995. Nevirapme alters the cleavage specificity of nbonuclease H of human immunodeficiency virus 1 reverse transcnptase. J. Biol. Chem. 270: 4861–4869.

    CAS  PubMed  Google Scholar 

  84. Mcdowall, K.J. and Cohen, S.N. N-termmal domain of the RNE gene product has RNase E activity and is non-overlapping with the argmme rich RNA-bmdmg site. J. Mol. Biol. 255: 349–355.

  85. Bork, P. and Sander, C. 1993. A hybrid protein kinase-RNase in an mterferon-mduced pathway? FEBS Letters 334: 149–152.

    CAS  PubMed  Google Scholar 

  86. Jmno, H., Ueda, M., Ozawa, S., Kikuchi, K., Ikeda, T., Enomoto, K., and Kitajima, M. 1996. Epidermal growth factor receptor-dependent cytotoxic effect by an EGF-nbonuclease conjugate on human cancer cell lines—a trial for less immunogenic chimeric toxin. Cancer Chemo. & Pharmacol. 38: 303–308.

    Google Scholar 

  87. Newton, D.L., Xue, Y., Olson, K.A., Fett, J.W., and Rybak, S.M. 1996. Angiogenm single-chain immunofusions—influence of peptide linkers and spacers between fusion protein domains. Biochem. 35: 545–543.

    CAS  Google Scholar 

  88. Melkohovets, Y.F. and Joshi, S. 1996. Fusion with an RNA binding domain to confer target RNA specificity to an RNase—design and engineering of TAT-RNase H that specifically recognizes and cleaves HIV-1 RNA in vitro. Nuc. Acids. Res. 24: 1908–1912.

    Google Scholar 

  89. Hertler, A.A. and Frankel, A.E. 1989. Immunotoxms' a clinical review of their use in the treatment of malignancies. J. Clin. Oncol. 7: 1932–1942.

    CAS  PubMed  Google Scholar 

  90. HoustonBiotechnology 4197X-RA

  91. Turnay, J., Olmo, N., Jimenez, A., Lizarbe, M.A., and Gavilanes, J.G. 1993. Kinetic study of the cytotoxic effect of alpha-sarcm, a nbosome inactivating protein from Aspergillus giganteus, on tumour cell lines: protein biosynthesis inhibition and cell binding. Mol. Cell. Biochem. 122: 39–47.

    CAS  PubMed  Google Scholar 

  92. Kijima, H., Ishida, H., Ohkawa, T., Kasham-Sabet, M., and Scanlon, K.J. 1995. Therapeutic applications of nbozymes. Pharm and Therapeutics 68: 247–267.

    CAS  Google Scholar 

  93. Usman, N., Beigelman, L. and McSwiggen, J.A. 1996. Hammerhead ribozyme engineering. Curr. Opin. Struct. Biol. 6: 527–533.

    CAS  PubMed  Google Scholar 

  94. Nakai, C., Konishi, A., Komatsu, Y., Inoue, H., Ohtsuka, E., and Kanaya, S. 1994. Sequence-specific cleavage of RNA by a hybrid rlbonuclease H. FEBS Letters 339: 67–72.

    CAS  PubMed  Google Scholar 

  95. Brown, J.W., Nolan, J.M., Haas, E.S., Rubio, M.A.T., Major, F., and Pace, N.R. 1996. Comparative sequence analysis of rlbonuclease P RNA using gene sequences from natural microbial populations reveals tertiary structural elements. Proc. Natl. Acad Sci. 93: 3001–3006.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Brown, J.W. 1996. The nbonuclease P database. Nuc. Acids. Res. 24: 236–237.

    CAS  Google Scholar 

  97. Liu, F. and Altman, S. 1995. Inhibition of viral gene expression by the catalytic RNA subunit of RNase P from Eschenchia coli . Genes & Devel. 9: 471–480.

    CAS  Google Scholar 

  98. Kufel, J. and Kirsebom, L.A. 1994. Cleavage site selection by M1 RNA,the catalytic subunit of Eschenchia coli RNase P, is influenced by pH. J. Mol. Biol. 244: 511–121.

    CAS  PubMed  Google Scholar 

  99. Truffert, J.C., Asselme, U., Brack, A., and Thuong, N.T., 1996. Synthesis, purification, and characterization of two peptide-oligonucleotide conjugates as potential artificial nucleases. Tetrahedron. 52: 3005–3016.

    CAS  Google Scholar 

  100. Bufe, A., Schramm, G., Petersen, A., Schlaak, M., and Becker, W.M. 1997. The function of allergens may determine allergemcrty. in New Horizons in Allergy Immunotherapy. Sehon, A, Kraft, D., and Hayglass, K.T. (eds). Plenum Publishing, New York, London, Washington DC, Moscow In press.

  101. Szewczak, A.A., Moore, P.B., Chang, Y.L., and Wool, I.G. 1993. The conformation of the sarcm/ncin loop from 28S nbosomal RNA. Proc. Natl. Acad. Sci. 90: 9581–9585.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Royo, J., Nas, N., Matton, D.P., Okamoto, S., Clarke, A.E., and Newbigm, E. 1996. A retroposon-like sequence linked to the S-locus of Nicotiana alatais expressed in styles in response to touch. Mol. Genet. 250: 180–188.

    CAS  Google Scholar 

  103. Sohlberg, B., Lundberg, U., Hartl, F.U. and Von Gabain, A., 1993. Functional interaction of heat shock protein Gro EL with an RNase E-like activity in Eschenchia coli . Proc. Natl. Acad. Sci. 90: 277–281.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Huynh, Q.K., Borgmeyer, J.R., Smith, C.E., Bell, L.D., and Shah, D.M. 1996. Isolation and characterization of a 30kDA protein with antifungal activity from leaves of Engelmanma pmnatifida . Biochem. J. 316: 723–727.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Wantanabe, Y., Ogawa, T., Takahashi, H., Ishida, I., Takeuchi, Y., Yamamoto, M., and Okada, Y. 1995. Resistance against multiple plant viruses in plants mediated by a double stranded-RNA specific nbonuclease. FEBS Letters 372: 165–168.

    Google Scholar 

  106. Youle, R.J., Wu, Y.N., Mikulski, S.M., Shogen, K., Hamilton, R.S., Newton, D. et al. 1994. RNase inhibition of human immunodeficiency virus infection of H9 cells. Proc. Natl. Acad. Sci. 91: 6012–6016.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Wang, L.M., Zhou, A.M., Vasavada, S., Dong, B.H., Nie, H.Q., Church, J.M. et al. 1995. Elevated levels of 2′,5′-lmked oligoadenylate-dependent nbonuclease L occur as an early event in colorectal tumongenesis. Clin. Cancer Res. 1: 1421–1428.

    CAS  PubMed  Google Scholar 

  108. Hubbell, H.R., Kanko, K., Suhadolnik, R.J., and Brodsky, I. 1994. RNase L and increased endonbonuclease activities in the mononuclear cells of patients with chronic myelogenous leukemia Anticancer Res. 14: 341–346.

    CAS  PubMed  Google Scholar 

  109. Suhadolnik, R.J., Reichenbach, N.L., Hitzges, P., Sobol, R.W., Peterson, D.L., Henry, B. et al. 1994. Upregulation of the 2—5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clin. Infect. Disease Suppl 1: 396–104.

    Google Scholar 

  110. Tomassmi, M., Magrmi, L., Bonmi, S., Lambiase, A., and Bonmi, S. 1994. Increased serum levels of eosmophil cationic protein and eosmophil-denved neurotoxm (protein X) in vernal keratoconjunctivitis. Ophthalmol. 101: 1808–1811.

    Google Scholar 

  111. Morley, D.J., Hodes, J.E., Calland, J., and Hodes, M.E. 1983. Immunohistochemical demonstration of nbonuclease and amylase in normal and neoplastic parotid glands. Hum. Pathol. 14: 969–973.

    CAS  PubMed  Google Scholar 

  112. Karawya, E.M. and Alwabel, A.H.A. 1996. Elevated levels of nbonucleases in serum of patients with liver disease. Saudi Medical J. 17: 42–46.

    Google Scholar 

  113. Barzilay, G., Walker, L.J., Robson, C.N., and Hickson, I.D. 1995. Site-directed mutagenesis of the human DNA repair enzyme HAP1 identification of residues important for AP endonuclease and RNase H activity. Nuc. Acids. Res. 23: 1544–1550.

    CAS  Google Scholar 

  114. Naskalski, J.W. 1989. Determination of rlbonuclease activity in serum of patients with pancreatic necrosis An attempt of extending the enzyme diagnosis of acute pancreatitis. Zeitschnft für medizimsche Laboratonums–diagnostik 30: 425–430.

    CAS  Google Scholar 

  115. Allmquant, B., Musenger, C., and Schuller, E. 1984. Intrathecal origin of CSF rlbonuclease Differences between infectious processes of the nervous system and multiple sclerosis. Ada Neurologica Scandmavica 70: 12–19.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Structural Biology, University of Texas Medical Branch, Galveston, TX, 77546–1157

    Catherine H. Schein

Authors
  1. Catherine H. Schein
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schein, C. From housekeeper to microsurgeon: The diagnostic and therapeutic potential of ribonucleases . Nat Biotechnol 15, 529–536 (1997). https://doi.org/10.1038/nbt0697-529

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt0697-529

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing