Human autoantibodies: probes for nucleolus structure and function

ConclusionsFour 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.

[1]  M. Sapp,et al.  DNA binding properties of a 110kDa nucleolar protein , 1986 .

[2]  M. Olson,et al.  Association of protein C23 with rapidly labeled nucleolar RNA. , 1986, Biochemistry.

[3]  W. Franke,et al.  A constitutive nucleolar protein identified as a member of the nucleoplasmin family. , 1987, The EMBO journal.

[4]  K. Messner,et al.  High sensitivity immunolocalization of double and single-stranded DNA by a monoclonal antibody. , 1987, European journal of cell biology.

[5]  E. Tan,et al.  Diversity of antinuclear antibodies in progressive systemic sclerosis. Anti-centromere antibody and its relationship to CREST syndrome. , 1980, Arthritis and rheumatism.

[6]  G. Reimer,et al.  Autoantibody to RNA polymerase I in scleroderma sera. , 1987, The Journal of clinical investigation.

[7]  R. Ochs,et al.  Localization of nucleolar phosphoproteins B23 and C23 during mitosis. , 1983, Experimental cell research.

[8]  O. Hornstein,et al.  Immunofluorescence studies in progressive systemic sclerosis (scleroderma) and mixed connective tissue disease , 1983, The British journal of dermatology.

[9]  W. Franke,et al.  Ribocharin: a nuclear Mr 40,000 protein specific to precursor particles of the large ribosomal subunit , 1985, Cell.

[10]  Sheldon Penman,et al.  Small RNA species of the HeLa cell: Metabolism and subcellular localization , 1976, Cell.

[11]  M. Mathews,et al.  Myositis autoantibody inhibits histidyl-tRNA synthetase: a model for autoimmunity , 1983, Nature.

[12]  S. Ghosh,et al.  The nucleolar structure. , 1976, International review of cytology.

[13]  I. Grummt,et al.  Formation of stable preinitiation complexes is a prerequisite for ribosomal DNA transcription in vitro. , 1983, Nucleic acids research.

[14]  R. Ochs,et al.  Fibrillarin: a new protein of the nucleolus identified by autoimmune sera , 1985, Biology of the cell.

[15]  G. Reimer,et al.  Correlates between autoantibodies to nucleolar antigens and clinical features in patients with systemic sclerosis (scleroderma). , 1988, Arthritis and rheumatism.

[16]  J. Bachellerie,et al.  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 , 1985, Cell.

[17]  R. Hazan,et al.  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-beta-D- ribofuranosylbenzimidazole , 1984, The Journal of cell biology.

[18]  R. Ritchie Antinucleolar antibodies. Their frequency and diagnostic association. , 1970, The New England journal of medicine.

[19]  Stephen M. Mount,et al.  Splicing of messenger RNA precursors is inhibited by antisera to small nuclear ribonucleoprotein , 1983, Cell.

[20]  K. Hadjiolova,et al.  Immunolocalization of nucleolar proteins after D-galactosamine-induced inhibition of transcription in rat hepatocytes. Maintenance of association of RNA polymerase I with inactivated nucleolar chromatin. , 1986, Experimental cell research.

[21]  M. Olson,et al.  Localization of phosphoprotein C23 in nucleoli by immunological methods. , 1981, Experimental cell research.

[22]  R. Richards,et al.  Localization of phosphoprotein C23 to nucleolar structures and to the nucleolus organizer regions. , 1981, Experimental cell research.

[23]  D. Hernandez-Verdun The nucleolar organizer regions , 1983 .

[24]  G. Reimer,et al.  Immunolocalization and partial characterization of a nucleolar autoantigen (PM-Scl) associated with polymyositis/scleroderma overlap syndromes. , 1986, Journal of immunology.

[25]  J. E. Stefano Purified lupus antigen la recognizes an oligouridylate stretch common to the 3′ termini of RNA polymerase III transcripts , 1984, Cell.

[26]  R. Moll,et al.  Immunological localization of a major karyoskeletal protein in nucleoli of oocytes and somatic cells of Xenopus laevis , 1982, The Journal of cell biology.

[27]  Stephen M. Mount,et al.  Small ribonucleoproteins from eukaryotes: structures and roles in RNA biogenesis. , 1983, Cold Spring Harbor symposia on quantitative biology.

[28]  W. Franke,et al.  Electron microscopic immunolocalization of a karyoskeletal protein of molecular weight 145 000 in nucleoli and perinucleolar bodies of Xenopus laevis. , 1984, Experimental cell research.

[29]  M. Thiry,et al.  Re‐evaluation of the site of transcription in Ehrlich tumour cell nucleoli , 1985, Biology of the cell.

[30]  W. Earnshaw,et al.  High titers of autoantibodies to topoisomerase I (Scl-70) in sera from scleroderma patients. , 1986, Science.

[31]  R. Hazan,et al.  Localization of ribosomal protein S1 in the granular component of the interphase nucleolus and its distribution during mitosis , 1985, The Journal of cell biology.

[32]  R. Ritchie Nucleolar structure by immunologic technics. , 1969, Cancer research.

[33]  G. Reimer,et al.  Immunolocalization of 7-2-ribonucleoprotein in the granular component of the nucleolus. , 1988, Experimental cell research.

[34]  H. Spring,et al.  A nucleolar skeleton of protein filaments demonstrated in amplified nucleoli of Xenopus laevis , 1981, The Journal of cell biology.

[35]  S. Jacob,et al.  Protein kinase activity of RNA polymerase I purified from a rat hepatoma: probable function of Mr 42,000 and 24,600 polypeptides. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Tom Maniatis,et al.  The role of small nuclear ribonucleoprotein particles in pre-mRNA splicing , 1987, Nature.

[37]  J. Steitz,et al.  Structural analysis of the human U3 ribonucleoprotein particle reveal a conserved sequence available for base pairing with pre-rRNA. , 1987, Molecular and cellular biology.

[38]  L. Rothblum,et al.  SnRNAs, SnRNPs, and RNA processing. , 1982, Annual review of biochemistry.

[39]  A. Beyer,et al.  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. , 1977, Biochemical and biophysical research communications.

[40]  J. Steitz,et al.  Sequential association of nucleolar 7-2 RNA with two different autoantigens. , 1983, The Journal of biological chemistry.

[41]  M. Christensen,et al.  Characterization of the nucleolar protein, B-36, using monoclonal antibodies. , 1986, Experimental cell research.

[42]  R. Reuter,et al.  Isolation and characterization of rabbit anti-m3 2,2,7G antibodies. , 1982, Nucleic acids research.

[43]  U. Scheer,et al.  Localization of RNA polymerase I in interphase cells and mitotic chromosomes by light and electron microscopic immunocytochemistry. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[44]  G. Morris,et al.  Monoclonal antibodies against a nucleolar protein from differentiating chick muscle cells. , 1985, Journal of cell science.

[45]  N. Gas,et al.  Correlation between rDNA transcription and distribution of a 100 kD nucleolar protein in CHO cells. , 1985, Experimental cell research.

[46]  I. Raška,et al.  Immunocytochemical localization of RNA polymerase I in the fibrillar centers of nucleoli , 1987 .

[47]  E. Tan,et al.  Identification of a nuclear protein (Scl-70) as a unique target of human antinuclear antibodies in scleroderma. , 1979, The Journal of biological chemistry.

[48]  G. Reimer,et al.  Monoclonal autoantibody from a (New Zealand black x New Zealand white)F1 mouse and some human scleroderma sera target an Mr 34,000 nucleolar protein of the U3 RNP particle. , 1987, Arthritis and rheumatism.

[49]  E. Tan,et al.  Antinucleolar antibodies in human sera. , 1973, Journal of immunology.

[50]  E. Tan,et al.  Autoantibodies to nuclear antigens (ANA): their immunobiology and medicine. , 1982, Advances in immunology.

[51]  E. Tan,et al.  Identification of ribosomal protein autoantigens. , 1985, Journal of immunology.

[52]  S. Jimenez,et al.  Topoisomerase I identified by scleroderma 70 antisera: enrichment of topoisomerase I at the centromere in mouse mitotic cells before anaphase. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[53]  H. Busch,et al.  Isolation and characterization of a human U3 small nucleolar RNA gene. , 1986, Biochemical and biophysical research communications.

[54]  W. Franke,et al.  Identification and localization of a novel nucleolar protein of high molecular weight by a monoclonal antibody. , 1984, Experimental cell research.

[55]  E. Tan,et al.  Detection of a nucleolar 7-2 ribonucleoprotein and a cytoplasmic 8-2 ribonucleoprotein with autoantibodies from patients with scleroderma. , 1983, The Journal of biological chemistry.

[56]  H. Bourbon,et al.  Nucleolin, the major nucleolar protein of growing eukaryotic cells: an unusual protein structure revealed by the nucleotide sequence. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[57]  K. Elkon,et al.  Lupus autoantibodies target ribosomal P proteins , 1985, The Journal of experimental medicine.

[58]  U. K. Laemmli,et al.  Mapping nucleolar proteins with monoclonal antibodies , 1984, The Journal of cell biology.

[59]  J. Steitz,et al.  U2 as well as U1 small nuclear ribonucleoproteins are involved in premessenger RNA splicing , 1985, Cell.

[60]  R. Cook,et al.  Purification and partial characterization of a nucleolar scleroderma antigen (Mr = 34,000; pI, 8.5) rich in NG,NG-dimethylarginine. , 1985, The Journal of biological chemistry.

[61]  D. Hernandez-Verdun,et al.  Fine structure of nucleoli in micronucleated cells. , 1979, Experimental cell research.

[62]  E. Tan,et al.  Association of antinuclear and antinucleolar antibodies in progressive systemic sclerosis. , 1982, Clinical and experimental immunology.

[63]  M. Tonato,et al.  Low molecular weight RNA associated with 28 s nucleolar RNA. , 1970, Journal of molecular biology.

[64]  G. Reimer,et al.  Inhibition of nucleolar reformation after microinjection of antibodies to RNA polymerase I into mitotic cells , 1987, The Journal of cell biology.