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Virchows Archiv B

, 54:131 | Cite as

Human autoantibodies: probes for nucleolus structure and function

  • Georg Reimer
  • Ivan Raška
  • Eng M. Tan
  • Ulrich Scheer
Review

Conclusions

Four distinct nucleolar proteins or RNA-protein complexes have recently been identified as targets of human autoimmune antibodies. These autoantigens areRNA polymer-ase I, PM-Scl (a particle possibly related to preribosomes), 7-2 RNP andfibrillarin (a U3-RNP associated protein). The four different nucleolar autoantigens could be assigned to distinct nucleolar subcompartments by light and electron microscopic immunocytochemistry. RNA polymerase I was located in the fibrillar centers, PM-Scl antigen and 7-2 RNP in the granular component and fibrillarin in the dense fibrillar component. Experimental evidence suggests that these naturally occurring antibodies could be helpful tools in further studying nucleolus structure and functions as well as molecular mechanisms involved in ribosome biogenesis.

From a clinical viewpoint, we believe that it is important to identify the nature of reactive autoantigens in systemic autoimmune diseases in order to answer questions concerning the mechanisms which render conserved ubiquitous cellular proteins immunogenic. Revealing such mechanisms in return could give clues with regard to the etiology of certain systemic rheumatic diseases. Ribosome biogenesis, a highly dynamic process with its many well-defined intermediate biological steps related to specific nuclear structures could be amenable for such studies.

Keywords

Scleroderma Ribosome Biogenesis Nucleolar Protein Granular Component Dense Fibrillar Component 
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.

References

  1. Bachellerie J-P, Michot B, Raynal F (1983) Recognition signals for mouse pre-rRNA processing. Mol Biol Rep 9:79–86PubMedCrossRefGoogle Scholar
  2. Benavente R, Krohne G, Stick R, Franke WW (1984) Electron microscopic immunolocalization of a karyoskeletal protein of molecular weight 145000 in nucleoli and prenucleolar bodies of Xenopus laevis. Exp Cell Res 151:224–235PubMedCrossRefGoogle Scholar
  3. Benavente R, Rose KM, Reimer G, Hügle-Dörr B, Scheer U (1987) Inhibition of nucleolar reformation after microinjection of antibodies to RNA polymerase I into mitotic cells. J Cell Biol 105 (in press)Google Scholar
  4. Bernstein RM, Steigerwald JC, Tan EM (1982) Association of antinuclear and antinucleolar antibodies in progressive systemic sclerosis. Clin Exp Immunol 48:43–51PubMedGoogle Scholar
  5. Black DL, Chabot B, Steitz JA (1985) U2 as well as U1 small nuclear ribonucleoproteins are involved in premessenger RNA splicing. Cell 42:737–750PubMedCrossRefGoogle Scholar
  6. Bourbon HM, Bugler B, Caizergues-Ferrer M, Almaric F, Zalta JP (1983) Maturation of a 100 kDa protein associated with preribosomes in Chinese hamster ovary cells. Mol Biol Rep9:39–47PubMedCrossRefGoogle Scholar
  7. Busch H, Smetana K (1970) The nucleolus. Academic Press, Inc New York, pp 1–626Google Scholar
  8. Busch H, Reddy R, Rothblum L, Choi YC (1982) SnRNAs, snRNPs, and RNA processing. Ann Rev Biochem 51:617–654PubMedCrossRefGoogle Scholar
  9. Busch H (1984) Nucleolar proteins: purification, isolation, and functional analyses. In: Hnilica (ed) Chromosomal nonhistone proteins. CRC Press, Inc, Boca Raton, Florida, pp 233–286Google Scholar
  10. Christensen ME, Beyer AL, Walker B, LeStourgeon WM (1977) Identification of NG, NG-dimethylarginine in a nuclear protein from the lower eukaryote Physarum polycephalum homologous to the major proteins of mammalian 40S ribonucleoprotein particles. Biochem Biophys Res Commun 74:621–625PubMedCrossRefGoogle Scholar
  11. Christensen ME, Moloo J, Swischuk JL, Schelling ME (1986) Characterization of the nucleolar protein, B-36, using monoclonal antibodies. Exp Cell Res 166:77–93PubMedCrossRefGoogle Scholar
  12. Crouch RJ, Kanaya S, Earl PL (1983) A model for the involvement of the small nucleolar RNA (U3) in processing eukaryotic ribosomal RNA. Mol Biol Rep 9:75–78PubMedCrossRefGoogle Scholar
  13. Douvas AS, Achten M, Tan EM (1979) Identification of a nuclear protein (Scl-70) as a unique target of human antinuclear antibodies in scleroderma. J Biol Chem 254:10514–10522PubMedGoogle Scholar
  14. Elkon KB, Parnasa AP, Foster CL (1985) Lupus autoantibodies target ribosomal P proteins. J Exp Med 162:459–471PubMedCrossRefGoogle Scholar
  15. Escande-Geraud ML, Azurn MC, Tichadou JL, Gas N (1985) Correlation between rDNA transcription and distribution of a 100 kD nucleolar protein in CHO cells. Exp Cell Res 161:353–363PubMedCrossRefGoogle Scholar
  16. Fakan S (1979) High resolution autoradiography studies on chromatin functions. In: Busch H (ed) The cell nucleus, vol 5: Academic Press Inc, New York, pp 3–53Google Scholar
  17. Francoeur A-M, Peebles CL, Heckman KJ, Lee JC, Tan EM (1985) Identification of ribosomal protein autoantigens. J Immunol 135:2378–2384PubMedGoogle Scholar
  18. Franke WW, Kleinschmidt JA, Spring H, Krohne G, Grund C, Trendelenburg MF, Stoehr M, Scheer U (1981) A nucleolar skeleton of protein filaments demonstrated in amplified nucleoli of Xenopus laevis. J Cell Biol 90:289–299PubMedCrossRefGoogle Scholar
  19. Goessens G (1984) Nucleolar structure. Int Rev Cytol 87:107–158PubMedCrossRefGoogle Scholar
  20. Grummt I, Maier U, Öhrlein A, Hassouna N, Bachellerie J-P (1985) Transcription of mouse rDNA terminates downstream of the 3′ end of 28S RNA and involves interaction of factors with repeated sequences in the 3′ spacer. Cell 43:801–810PubMedCrossRefGoogle Scholar
  21. Guldner HH, Szostecki C, Vosberg HP, Lakomek HJ, Penner E, Bautz FA (1986) Scl 70 autoantibodies from scleroderma patients recognize a 95 kDa protein identified as DNA topoisomerase I. Chromosoma (Berl) 94:132–138CrossRefGoogle Scholar
  22. Hadjiolov AA (1985) The nucleolus and ribosome biogenesis. Cell biol monographs, vol 12, Springer, Berlin Heidelberg New York Tokyo, pp 1–268Google Scholar
  23. Hadjiolova K, Rose KM, Scheer U (1986) Immunolocalization of nucleolar proteins after D-galactosamine-induced inhibition of transcription in rat hepatocytes. Exp Cell Res 165:481–493PubMedCrossRefGoogle Scholar
  24. Hashimoto C, Steitz JA (1983) Sequential association of nucleolar 7-2 RNA with two different autoantigens. J Biol Chem 258:1379–1382PubMedGoogle Scholar
  25. Hernandez-Verdun D, Bouteille M, Ege T, Ringertz NR (1979) Fine structure of nucleoli in micronucleated cells. Exp Cell Res 124:223–235PubMedCrossRefGoogle Scholar
  26. Hernandez-Verdun D (1983) The nucleolar organizer region. Biol Cell 49:191–202Google Scholar
  27. Herrera AH, Olson MOJ (1986) Association of protein C23 with rapidly labeled nucleolar RNA. Biochem J 25:6258–6264CrossRefGoogle Scholar
  28. Hügle B, Hazan R, Scheer U, Franke WW (1985a) Localization of ribosomal protein S1 in the granular component of the interphase nucleolus and its distribution during mitosis. J Cell Biol 100:873–886PubMedCrossRefGoogle Scholar
  29. Hügle B, Scheer U, Franke WW (1985b) Ribocharin: a nuclear Mr 40000 protein specific to precursor particles of the large ribosomal subunit. Cell 41:615–627PubMedCrossRefGoogle Scholar
  30. Kalden JR, Feltkamp TEW (eds) (1982) Antibodies to nuclear antigens. Immunological specificity and clinical implications. Exerpta Medica, Amsterdam-Oxford-PrincetonGoogle Scholar
  31. Kistler J, Duncombe Y, Laemmli UK (1984) Mapping nucleolar proteins with monoclonal antibodies. J Cell Biol 99:1981–1988PubMedCrossRefGoogle Scholar
  32. Krohne G, Stick R, Kleinschmidt JA, Moll R, Franke WW, Hausen P (1982) Immunological localization of a major karyoskeletal protein in nucleoli of oocytes and somatic cells of Xenopus laevis. J Cell Biol 94:749–754PubMedCrossRefGoogle Scholar
  33. Lacoste-Royal G, Simard R (1984) Distribution of U3 snRNA in the nucleolus of CHO cells. Biol Cell 52:191–194PubMedGoogle Scholar
  34. Lapeyre B, Bourbon H, Amalric F (1987) Nucleolin, the major nucleolar protein of growing eukaryotic cells: an unusual protein structure revealed by the nucleotide sequence. Proc Natl Acad Sci USA 84:1472–1476PubMedCrossRefGoogle Scholar
  35. Lischwe MA, Richards RL, Busch RK, Busch H (1981) Localization of phosphoprotein C23 to nucleolar structures and the nucleolar organizing regions. Exp Cell Res 136:101–109PubMedCrossRefGoogle Scholar
  36. Lischwe MA, Ochs RL, Reddy R, Cook RG, Yeoman LC, Tan EM, Reichlin M, Busch H (1985) Purification and partial characterization of a nucleolar scleroderma antigen (Mr = 34000; pI, 8.5) rich in NG, NG-dimethylarginine. J Biol Chem 260:14304–14310PubMedGoogle Scholar
  37. Lührmann R, Appel B, Bringmann P, Rinke J, Reuter R, Rothe S (1982) Isolation and characterization of rabbit antim2’2’7G antibodies. Nucl Acids Res 10:7103–7113PubMedCrossRefGoogle Scholar
  38. Maniatis T, Reed R (1987) The role of small nuclear ribonucleoprotein particles in pre-mRNA splicing. Nature 325:673–678PubMedCrossRefGoogle Scholar
  39. Mathews MB, Bernstein RM (1983) Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity. Nature 304:177–179PubMedCrossRefGoogle Scholar
  40. Mathews MB, Reichlin M, Hughes GRV, Bernstein RM (1984) Antithreonyl-tRNA synthetase, a second myositis related autoantibody. J Exp Med 160:420–434PubMedCrossRefGoogle Scholar
  41. Maul GG, French BT, van Venrooij WJ, Jiminez SA (1986) Topoisomerase I identified by scleroderma-70 antisera, enrichment of topoisomerase I at the centromere in mouse mitotic cells before anaphase. Proc Natl Acad Sci USA 83:5145–5149PubMedCrossRefGoogle Scholar
  42. Morris GE, Man N, Head LP (1985) Monoclonal antibodies against a nucleolar protein from differentiating chick muscles cells. J Cell Sci 76:105–113PubMedGoogle Scholar
  43. Ochs RL, Lischwe MA, O’Leary P, Busch H (1983) Localization of nucleolar phosphoproteins B23 and C23 during mitosis. Exp Cell Res 146:139–149PubMedCrossRefGoogle Scholar
  44. Ochs RL, Lischwe MA, Spohn WH, Busch H (1985) Fibrillarin: a new protein of the nucleolus identified by autoimmune sera. Biol Cell 54:123–134PubMedGoogle Scholar
  45. Olson MOJ, Guetzow K, Busch H (1981) Localization of phosphoprotein C23 in nucleoli by immunological methods. Exp Cell Res 135:259–265PubMedCrossRefGoogle Scholar
  46. Padgett RA, Mount SM, Steitz JA, Sharp PA (1983) Splicing of messenger RNA precursors is inhibited by antisera to small nuclear ribonucleoprotein. Cell 35:101–107PubMedCrossRefGoogle Scholar
  47. Parker KA, Steitz JA (1987) Structural analyses of the human U3 ribonucleoprotein particle reveal a conserved sequence available for base-pairing with pre-rRNA. Mol Cell Biol 7:2899–2913PubMedGoogle Scholar
  48. Pinnas JL, Northway JD, Tan EM (1973) Antinucleolar antibodies in human sera. J Immunol 111: 996–1004PubMedGoogle Scholar
  49. Prestayko AW, Tonato M, Busch H (1970) Low molecular weight RNA associated with 28S nucleolar RNA. J Mol Biol 47:505–515PubMedCrossRefGoogle Scholar
  50. Reddy R, Tan EM, Henning D, Nogha K, Busch H (1983) Detection of nucleolar 7-2 ribonucleoprotein and a cytoplasmic 8-2 ribonucleoprotein with autoantibodies from patients with scleroderma. J Biol Chem 258:1383–1386PubMedGoogle Scholar
  51. Reichlin M, Maddison PJ, Targoff I, Bunch T, Arnett F, Sharp G, Treadwell E, Tan EM (1984) Antibodies to a nuclear/ nucleolar antigen in patients with polymyositis overlap syndromes. J Clin Immunol 4:40PubMedCrossRefGoogle Scholar
  52. Reimer G, Huschka U, Keller J, Kammerer R, Hornstein OP (1983) Immunofluorescence studies in progressive systemic sclerosis (scleroderma) and mixed connective tissue disease. Br JDermatol 109:27–36CrossRefGoogle Scholar
  53. Reimer G, Scheer U, Peters J-M, Tan EM (1986) Immunolocalization and partial characterization of a nucleolar autoantigen (PM-Scl) associated with polymyositis/scleroderma overlap syndromes. J Immunol 137:3802–3808PubMedGoogle Scholar
  54. Reimer G, Rose KM, Scheer U, Tan EM (1987a) Autoantibody to RNA polymerase I in scleroderma sera. J Clin Invest 79:65–72PubMedCrossRefGoogle Scholar
  55. Reimer G, Pollard KM, Penning CA, Ochs RL, Lischwe MA, Busch H, Tan EM (1987b) Monoclonal autoantibody from NZB/NZW F1 mouse and some human scleroderma sera target at Mr 34000 nucleolar protein of the U3-ribonucleoprotein particle. Arthritis Rheum 30:793–800PubMedCrossRefGoogle Scholar
  56. Reimer G, Steen VD, Penning CA, Medsger TA, Tan EM (1987c) Correlates between autoantibodies to nucleolar antigens and clinical features in patients with systemic sclerosis. Arthritis Rheum (in press)Google Scholar
  57. Reimer G, Scheer U, Tan EM (1987d) Immunolocalization of 7-2 ribonucleoprotein in the granular component of the nucleolus. Exp Cell Res (in press)Google Scholar
  58. Ritchie RF (1969) Nucleolar structure by immunologic techniques. Cancer Res 29:267–269PubMedGoogle Scholar
  59. Ritchie RF (1970) Antinucleolar antibodies: their frequency and diagnostic association. N Engl J Med 282:1174–1178PubMedGoogle Scholar
  60. Ringertz NR, Ege T, Carlsson S-A (1973) Nucleolus specific antigens in human fibroblast and hybrid cells studied with patient autoantibodies. In: Kulonen E, Pikarainen QJ (eds) Biology of the fibroblast. Academic Press, New York, pp 189–194Google Scholar
  61. Rose KM, Stetler DA, Jacob ST (1981) Protein kinase activity of RNA polymerase I purified from rat hepatoma: probable function of Mr 42000 and 46000 polypeptides. Proc Natl Acad Sci USA 78:2833–2837PubMedCrossRefGoogle Scholar
  62. Rose KM, Stetler DA, Jacob ST (1983) RNA polymerases from higher eukaryotes. In: Jacob ST (ed) Enzymes of nucleic acid synthesis and modification. CRC Press, Inc, Boca Raton, Florida, 43–74Google Scholar
  63. Sapp M, Knippers R, Richter R (1986) DNA binding properties of a 110 kDa nucleolar protein. Nucl Acid Res 14:6803–6820CrossRefGoogle Scholar
  64. Scheer U, Hügle B, Hazan R, Rose KM (1984) Drug-induced dispersal of transcribed rRNA genes and transcriptional products: immunolocalization and silver staining of different nucleolar components in rat cells treated with 5,6-dichloro-β-D-ribofuranosylbenzimidazole. J Cell Biol 99:672–679PubMedCrossRefGoogle Scholar
  65. Scheer U, Rose KM (1984) Localization of RNA polymerase I in interphase cells and mitotic chromosomes by light and electron microscopic immunocytochemistry. Proc Natl Acad Sci USA 81:1431–1435PubMedCrossRefGoogle Scholar
  66. Scheer U, Messner K, Hazan R, Raska I, Hansmann P, Falk H, Spiess E, Franke WW (1987) High sensitivity immunolocalization of double and single-stranded DNA by a monoclonal antibody. Eur J Cell Biol 43:358–371PubMedGoogle Scholar
  67. Scheer U, Raska I (1987) Immunocytochemical localization of RNA polymerase I in the fibrillar centers of nucleoli. Chromosomes Today 9:284–294Google Scholar
  68. Schmidt-Zachmann MS, Hügle B, Scheer U, Franke WW (1984) Identification and localization of a novel nucleolar protein of high molecular weight by a monoclonal antibody. Exp Cell Res 153:327–346PubMedCrossRefGoogle Scholar
  69. Schmidt-Zachmann MS, Hügle-Dörr B, Franke WW (1987) A constitutive nucleolar protein identified as a member of the nucleoplasmin family. EMBO J 6:1881–1890PubMedGoogle Scholar
  70. Seelig HP (1983) Antikörper gegen Zellkernantigene. Gustav Fischer Verlag, Stuttgart, New YorkGoogle Scholar
  71. Shero JH, Bordwell B, Rothfield NF, Earnshaw WC (1986) High titers of autoantibodies to topoisomerase I (Scl-70) in sera from scleroderma patients. Science 231:737–740PubMedCrossRefGoogle Scholar
  72. Spector DL, Ochs RL, Busch H (1984) Silver staining, immunofluorescence, and immunelectron microscopic localization of nucleolar phosphoproteins B23 and C23. Chromosoma (Berl) 90:139–148CrossRefGoogle Scholar
  73. Stefano J (1984) Purified lupus antigen La recognizes an oligouridylate stretch common to the 3′termini of RNA polymerase III transcripts. Cell 36:145–154PubMedCrossRefGoogle Scholar
  74. Steitz JA, Wolin SL, Rinke J, Petterson I, Mount SM, Lerner EA, Hinterberger M, Gottlieb E (1983) Small ribonucleoproteins from eukaryotes: structures and roles in RNA biogenesis. Cold Spring Harbor Symp Quant Biol 47:893–900PubMedGoogle Scholar
  75. Suh D, Busch H, Reddy R (1986) Isolation and characterization of a human U3 small nucleolar gene. Biochem Res Comm 137:1133–1140CrossRefGoogle Scholar
  76. Tague BW, Gerbi SA (1984) Processing of the large rRNA precursor: Two proposed categories of RNA-RNA interactions in eukaryotes. J Mol Evol 20:362–367PubMedCrossRefGoogle Scholar
  77. Tan EM, Rodnan GP, Garcia I, Moroi Y, Fritzler MJ, Peebles C (1980) Diversity of antinuclear antibodies in progressive systemic sclerosis. Anti-centromere antibody and its relationship to CREST syndrome. Arthritis Rheum 23:617–625PubMedCrossRefGoogle Scholar
  78. Tan EM (1982) Autoantibodies to nuclear antigens (ANA): their immunobiology and medicine. Adv Immunol 33:167–240PubMedCrossRefGoogle Scholar
  79. Thiry M, Lepoint A, Goessens G (1985) Re-evaluation of the site of transcription in Ehrlich tumor cell nucleoli. Biol Cell 54:57–64PubMedGoogle Scholar
  80. Tokuyasu KT (1980) Immunocytochemistry on ultrathin frozen sections. Histochem J 12:381–403PubMedCrossRefGoogle Scholar
  81. Vaughan MA (1987) An autoimmune antibody from scleroderma patients recognize a component of the plant cell nucleolus. Histochem J 86:533–535CrossRefGoogle Scholar
  82. Wandelt C, Grummt I (1983) Formation of stable preinitiation complexes is a prerequisite for ribosomal DNA transcription in vitro. Nucl Acids Res 11:3795–3809PubMedCrossRefGoogle Scholar
  83. Zieve G, Penman S (1976) Small RNA species of the HeLa cell: metabolism and subcellular localization. Cell 8:19–31PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • Georg Reimer
    • 1
  • Ivan Raška
    • 2
  • Eng M. Tan
    • 3
  • Ulrich Scheer
    • 4
  1. 1.Department of DermatologyUniversity of Erlangen-NürnbergErlangenFederal Republic of Germany
  2. 2.Institute of Experimental MedicineCzechoslovak Academy of SciencesPragueCSSR
  3. 3.W.M. Keck Foundation Autoimmune Disease CenterScripps Clinic and Research FoundationLa JollaUSA
  4. 4.Institute of Zoology IUniversity of WürzburgWürzburgFederal Republic of Germany

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