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Human autoantibodies: probes for nucleolus structure and function

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Virchows Archiv B

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.

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References

  • Bachellerie J-P, Michot B, Raynal F (1983) Recognition signals for mouse pre-rRNA processing. Mol Biol Rep 9:79–86

    Article  PubMed  CAS  Google Scholar 

  • 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 151:224–235

    Article  PubMed  CAS  Google Scholar 

  • 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)

  • Bernstein RM, Steigerwald JC, Tan EM (1982) Association of antinuclear and antinucleolar antibodies in progressive systemic sclerosis. Clin Exp Immunol 48:43–51

    PubMed  CAS  Google Scholar 

  • Black DL, Chabot B, Steitz JA (1985) U2 as well as U1 small nuclear ribonucleoproteins are involved in premessenger RNA splicing. Cell 42:737–750

    Article  PubMed  CAS  Google Scholar 

  • 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 Rep9:39–47

    Article  PubMed  CAS  Google Scholar 

  • Busch H, Smetana K (1970) The nucleolus. Academic Press, Inc New York, pp 1–626

    Google Scholar 

  • Busch H, Reddy R, Rothblum L, Choi YC (1982) SnRNAs, snRNPs, and RNA processing. Ann Rev Biochem 51:617–654

    Article  PubMed  CAS  Google Scholar 

  • Busch H (1984) Nucleolar proteins: purification, isolation, and functional analyses. In: Hnilica (ed) Chromosomal nonhistone proteins. CRC Press, Inc, Boca Raton, Florida, pp 233–286

    Google Scholar 

  • 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 74:621–625

    Article  PubMed  CAS  Google Scholar 

  • Christensen ME, Moloo J, Swischuk JL, Schelling ME (1986) Characterization of the nucleolar protein, B-36, using monoclonal antibodies. Exp Cell Res 166:77–93

    Article  PubMed  CAS  Google Scholar 

  • 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 9:75–78

    Article  PubMed  CAS  Google Scholar 

  • 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 254:10514–10522

    PubMed  CAS  Google Scholar 

  • Elkon KB, Parnasa AP, Foster CL (1985) Lupus autoantibodies target ribosomal P proteins. J Exp Med 162:459–471

    Article  PubMed  CAS  Google Scholar 

  • 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 161:353–363

    Article  PubMed  CAS  Google Scholar 

  • 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 3–53

    Google Scholar 

  • Francoeur A-M, Peebles CL, Heckman KJ, Lee JC, Tan EM (1985) Identification of ribosomal protein autoantigens. J Immunol 135:2378–2384

    PubMed  CAS  Google Scholar 

  • 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 90:289–299

    Article  PubMed  CAS  Google Scholar 

  • Goessens G (1984) Nucleolar structure. Int Rev Cytol 87:107–158

    Article  PubMed  CAS  Google Scholar 

  • 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 43:801–810

    Article  PubMed  CAS  Google Scholar 

  • 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) 94:132–138

    Article  CAS  Google Scholar 

  • Hadjiolov AA (1985) The nucleolus and ribosome biogenesis. Cell biol monographs, vol 12, Springer, Berlin Heidelberg New York Tokyo, pp 1–268

    Google Scholar 

  • Hadjiolova K, Rose KM, Scheer U (1986) Immunolocalization of nucleolar proteins after D-galactosamine-induced inhibition of transcription in rat hepatocytes. Exp Cell Res 165:481–493

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto C, Steitz JA (1983) Sequential association of nucleolar 7-2 RNA with two different autoantigens. J Biol Chem 258:1379–1382

    PubMed  CAS  Google Scholar 

  • Hernandez-Verdun D, Bouteille M, Ege T, Ringertz NR (1979) Fine structure of nucleoli in micronucleated cells. Exp Cell Res 124:223–235

    Article  PubMed  CAS  Google Scholar 

  • Hernandez-Verdun D (1983) The nucleolar organizer region. Biol Cell 49:191–202

    Google Scholar 

  • Herrera AH, Olson MOJ (1986) Association of protein C23 with rapidly labeled nucleolar RNA. Biochem J 25:6258–6264

    Article  CAS  Google Scholar 

  • 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 100:873–886

    Article  PubMed  Google Scholar 

  • Hügle B, Scheer U, Franke WW (1985b) Ribocharin: a nuclear Mr 40000 protein specific to precursor particles of the large ribosomal subunit. Cell 41:615–627

    Article  PubMed  Google Scholar 

  • Kalden JR, Feltkamp TEW (eds) (1982) Antibodies to nuclear antigens. Immunological specificity and clinical implications. Exerpta Medica, Amsterdam-Oxford-Princeton

    Google Scholar 

  • Kistler J, Duncombe Y, Laemmli UK (1984) Mapping nucleolar proteins with monoclonal antibodies. J Cell Biol 99:1981–1988

    Article  PubMed  CAS  Google Scholar 

  • 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 94:749–754

    Article  PubMed  CAS  Google Scholar 

  • Lacoste-Royal G, Simard R (1984) Distribution of U3 snRNA in the nucleolus of CHO cells. Biol Cell 52:191–194

    PubMed  CAS  Google Scholar 

  • 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 84:1472–1476

    Article  PubMed  CAS  Google Scholar 

  • Lischwe MA, Richards RL, Busch RK, Busch H (1981) Localization of phosphoprotein C23 to nucleolar structures and the nucleolar organizing regions. Exp Cell Res 136:101–109

    Article  PubMed  CAS  Google Scholar 

  • 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 260:14304–14310

    PubMed  CAS  Google Scholar 

  • 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 10:7103–7113

    Article  PubMed  Google Scholar 

  • Maniatis T, Reed R (1987) The role of small nuclear ribonucleoprotein particles in pre-mRNA splicing. Nature 325:673–678

    Article  PubMed  CAS  Google Scholar 

  • Mathews MB, Bernstein RM (1983) Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity. Nature 304:177–179

    Article  PubMed  CAS  Google Scholar 

  • Mathews MB, Reichlin M, Hughes GRV, Bernstein RM (1984) Antithreonyl-tRNA synthetase, a second myositis related autoantibody. J Exp Med 160:420–434

    Article  PubMed  CAS  Google Scholar 

  • 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 83:5145–5149

    Article  PubMed  CAS  Google Scholar 

  • Morris GE, Man N, Head LP (1985) Monoclonal antibodies against a nucleolar protein from differentiating chick muscles cells. J Cell Sci 76:105–113

    PubMed  CAS  Google Scholar 

  • Ochs RL, Lischwe MA, O’Leary P, Busch H (1983) Localization of nucleolar phosphoproteins B23 and C23 during mitosis. Exp Cell Res 146:139–149

    Article  PubMed  CAS  Google Scholar 

  • Ochs RL, Lischwe MA, Spohn WH, Busch H (1985) Fibrillarin: a new protein of the nucleolus identified by autoimmune sera. Biol Cell 54:123–134

    PubMed  CAS  Google Scholar 

  • Olson MOJ, Guetzow K, Busch H (1981) Localization of phosphoprotein C23 in nucleoli by immunological methods. Exp Cell Res 135:259–265

    Article  PubMed  CAS  Google Scholar 

  • Padgett RA, Mount SM, Steitz JA, Sharp PA (1983) Splicing of messenger RNA precursors is inhibited by antisera to small nuclear ribonucleoprotein. Cell 35:101–107

    Article  PubMed  CAS  Google Scholar 

  • 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 7:2899–2913

    PubMed  CAS  Google Scholar 

  • Pinnas JL, Northway JD, Tan EM (1973) Antinucleolar antibodies in human sera. J Immunol 111: 996–1004

    PubMed  CAS  Google Scholar 

  • Prestayko AW, Tonato M, Busch H (1970) Low molecular weight RNA associated with 28S nucleolar RNA. J Mol Biol 47:505–515

    Article  PubMed  CAS  Google Scholar 

  • 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 258:1383–1386

    PubMed  CAS  Google Scholar 

  • 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 4:40

    Article  PubMed  CAS  Google Scholar 

  • 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 109:27–36

    Article  CAS  Google Scholar 

  • 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 137:3802–3808

    PubMed  CAS  Google Scholar 

  • Reimer G, Rose KM, Scheer U, Tan EM (1987a) Autoantibody to RNA polymerase I in scleroderma sera. J Clin Invest 79:65–72

    Article  PubMed  CAS  Google Scholar 

  • 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 30:793–800

    Article  PubMed  CAS  Google Scholar 

  • 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)

  • Reimer G, Scheer U, Tan EM (1987d) Immunolocalization of 7-2 ribonucleoprotein in the granular component of the nucleolus. Exp Cell Res (in press)

  • Ritchie RF (1969) Nucleolar structure by immunologic techniques. Cancer Res 29:267–269

    PubMed  CAS  Google Scholar 

  • Ritchie RF (1970) Antinucleolar antibodies: their frequency and diagnostic association. N Engl J Med 282:1174–1178

    PubMed  CAS  Google Scholar 

  • 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 189–194

    Google Scholar 

  • 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 78:2833–2837

    Article  PubMed  CAS  Google Scholar 

  • 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, 43–74

    Google Scholar 

  • Sapp M, Knippers R, Richter R (1986) DNA binding properties of a 110 kDa nucleolar protein. Nucl Acid Res 14:6803–6820

    Article  CAS  Google Scholar 

  • 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 99:672–679

    Article  PubMed  CAS  Google Scholar 

  • 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 81:1431–1435

    Article  PubMed  CAS  Google Scholar 

  • 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 43:358–371

    PubMed  CAS  Google Scholar 

  • Scheer U, Raska I (1987) Immunocytochemical localization of RNA polymerase I in the fibrillar centers of nucleoli. Chromosomes Today 9:284–294

    Google Scholar 

  • 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 153:327–346

    Article  PubMed  CAS  Google Scholar 

  • Schmidt-Zachmann MS, Hügle-Dörr B, Franke WW (1987) A constitutive nucleolar protein identified as a member of the nucleoplasmin family. EMBO J 6:1881–1890

    PubMed  CAS  Google Scholar 

  • Seelig HP (1983) Antikörper gegen Zellkernantigene. Gustav Fischer Verlag, Stuttgart, New York

    Google Scholar 

  • Shero JH, Bordwell B, Rothfield NF, Earnshaw WC (1986) High titers of autoantibodies to topoisomerase I (Scl-70) in sera from scleroderma patients. Science 231:737–740

    Article  PubMed  CAS  Google Scholar 

  • Spector DL, Ochs RL, Busch H (1984) Silver staining, immunofluorescence, and immunelectron microscopic localization of nucleolar phosphoproteins B23 and C23. Chromosoma (Berl) 90:139–148

    Article  CAS  Google Scholar 

  • Stefano J (1984) Purified lupus antigen La recognizes an oligouridylate stretch common to the 3′termini of RNA polymerase III transcripts. Cell 36:145–154

    Article  PubMed  CAS  Google Scholar 

  • 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 47:893–900

    PubMed  Google Scholar 

  • Suh D, Busch H, Reddy R (1986) Isolation and characterization of a human U3 small nucleolar gene. Biochem Res Comm 137:1133–1140

    Article  CAS  Google Scholar 

  • Tague BW, Gerbi SA (1984) Processing of the large rRNA precursor: Two proposed categories of RNA-RNA interactions in eukaryotes. J Mol Evol 20:362–367

    Article  PubMed  CAS  Google Scholar 

  • 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 23:617–625

    Article  PubMed  CAS  Google Scholar 

  • Tan EM (1982) Autoantibodies to nuclear antigens (ANA): their immunobiology and medicine. Adv Immunol 33:167–240

    Article  PubMed  CAS  Google Scholar 

  • Thiry M, Lepoint A, Goessens G (1985) Re-evaluation of the site of transcription in Ehrlich tumor cell nucleoli. Biol Cell 54:57–64

    PubMed  CAS  Google Scholar 

  • Tokuyasu KT (1980) Immunocytochemistry on ultrathin frozen sections. Histochem J 12:381–403

    Article  PubMed  CAS  Google Scholar 

  • Vaughan MA (1987) An autoimmune antibody from scleroderma patients recognize a component of the plant cell nucleolus. Histochem J 86:533–535

    Article  CAS  Google Scholar 

  • Wandelt C, Grummt I (1983) Formation of stable preinitiation complexes is a prerequisite for ribosomal DNA transcription in vitro. Nucl Acids Res 11:3795–3809

    Article  PubMed  CAS  Google Scholar 

  • Zieve G, Penman S (1976) Small RNA species of the HeLa cell: metabolism and subcellular localization. Cell 8:19–31

    Article  PubMed  CAS  Google Scholar 

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Reimer, G., Raška, I., Tan, E.M. et al. Human autoantibodies: probes for nucleolus structure and function. Virchows Archiv B Cell Pathol 54, 131–143 (1987). https://doi.org/10.1007/BF02899205

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