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Anti-RNA polymerase antibodies in systemic sclerosis (SSc): association with anti-topoisomerase I antibodies and identification of autoreactive subunits of RNA polymerase II. 1996

G R Harvey, and A L Rands, and N J McHugh
Bath Institute for Rheumatic Diseases, Trimbridge, UK.

The prevalence of autoantibodies to the three RNA polymerase (RNAP) enzymes in the sera of 249 SSc patients was measured using the technique of immunoprecipitation of 35S-methionine-labelled K562 cell extracts. Forty-six anti-RNAP sera were detected (18.5%) and three main groups were identified: anti-RNAP I/III sera (10; 4.0%), anti-RNAP I/II/III sera (15; 6.0%), and sera precipitating the phosphorylated (IIO) form of RNAP II (18; 7.2%). All sera in the third group also precipitated topoisomerase I (topo I), and six of them also precipitated the unphosphorylated (IIA) form of RNAP II. Although RNAP II/topo I multienzyme complexes may occur in cell extracts, autoreactive epitopes were shown to be located on both enzymes by a combination of antigen depletion studies, and in vitro assays which demonstrated functional inhibition of topo I activity. Furthermore, immunoblotting experiments using affinity-purified extracts demonstrated that all sera with anti-RNAP II antibodies recognized the largest RNAP II subunit in its phosphorylated form (IIo; 240 kD), whereas the unphosphorylated subunit (IIa; 220 kD) was only recognized by sera which also precipitated RNAP IIA. Therefore at least two different sites on the largest subunit of RNAP II are recognized by SSc sera, and one of these sites is unique to the phosphorylated (IIO) form.

UI MeSH Term Description Entries
D004264 DNA Topoisomerases, Type I DNA TOPOISOMERASES that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. DNA Topoisomerases, Type I enzymes reduce the topological stress in the DNA structure by relaxing the superhelical turns and knotted rings in the DNA helix. DNA Nicking-Closing Protein,DNA Relaxing Enzyme,DNA Relaxing Protein,DNA Topoisomerase,DNA Topoisomerase I,DNA Topoisomerase III,DNA Topoisomerase III alpha,DNA Topoisomerase III beta,DNA Untwisting Enzyme,DNA Untwisting Protein,TOP3 Topoisomerase,TOP3alpha,TOPO IIIalpha,Topo III,Topoisomerase III,Topoisomerase III beta,Topoisomerase IIIalpha,Topoisomerase IIIbeta,DNA Nicking-Closing Proteins,DNA Relaxing Enzymes,DNA Type 1 Topoisomerase,DNA Untwisting Enzymes,DNA Untwisting Proteins,Topoisomerase I,Type I DNA Topoisomerase,III beta, Topoisomerase,III, DNA Topoisomerase,III, Topo,III, Topoisomerase,IIIalpha, TOPO,IIIalpha, Topoisomerase,IIIbeta, Topoisomerase,Topoisomerase III, DNA,Topoisomerase, TOP3,beta, Topoisomerase III
D005779 Immunodiffusion Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. Gel Diffusion Tests,Diffusion Test, Gel,Diffusion Tests, Gel,Gel Diffusion Test,Immunodiffusions,Test, Gel Diffusion,Tests, Gel Diffusion
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000937 Antigen-Antibody Reactions The processes triggered by interactions of ANTIBODIES with their ANTIGENS. Antigen Antibody Reactions,Antigen-Antibody Reaction,Reaction, Antigen-Antibody,Reactions, Antigen-Antibody
D001323 Autoantibodies Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them. Autoantibody
D001324 Autoantigens Endogenous tissue constituents with the ability to interact with AUTOANTIBODIES and cause an immune response. Autoantigen,Autologous Antigen,Autologous Antigens,Self-Antigen,Self-Antigens,Antigen, Autologous,Antigens, Autologous,Self Antigen,Self Antigens
D012319 RNA Polymerase II A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 2.7.7.6. DNA-Dependent RNA Polymerase II,RNA Pol II,RNA Polymerase B,DNA Dependent RNA Polymerase II
D012595 Scleroderma, Systemic A chronic multi-system disorder of CONNECTIVE TISSUE. It is characterized by SCLEROSIS in the SKIN, the LUNGS, the HEART, the GASTROINTESTINAL TRACT, the KIDNEYS, and the MUSCULOSKELETAL SYSTEM. Other important features include diseased small BLOOD VESSELS and AUTOANTIBODIES. The disorder is named for its most prominent feature (hard skin), and classified into subsets by the extent of skin thickening: LIMITED SCLERODERMA and DIFFUSE SCLERODERMA. Sclerosis, Systemic,Systemic Scleroderma,Systemic Sclerosis
D015151 Immunoblotting Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies. Dot Immunoblotting,Electroimmunoblotting,Immunoelectroblotting,Reverse Immunoblotting,Immunoblotting, Dot,Immunoblotting, Reverse,Dot Immunoblottings,Electroimmunoblottings,Immunoblottings,Immunoblottings, Dot,Immunoblottings, Reverse,Immunoelectroblottings,Reverse Immunoblottings
D059004 Topoisomerase I Inhibitors Compounds that inhibit the activity of DNA TOPOISOMERASE I. DNA Topoisomerase I Inhibitor,DNA Topoisomerase III Inhibitor,DNA Topoisomerase III Inhibitors,DNA Type 1 Topoisomerase Inhibitor,DNA Type III Topoisomerase Inhibitor,DNA Type III Topoisomerase Inhibitors,Topoisomerase 1 Inhibitor,Topoisomerase 1 Inhibitors,Topoisomerase 3 Inhibitor,Topoisomerase 3 Inhibitors,Topoisomerase I Inhibitor,Topoisomerase III Inhibitor,Topoisomerase III Inhibitors,DNA Topoisomerase I Inhibitors,DNA Type 1 Topoisomerase Inhibitors,1 Inhibitor, Topoisomerase,3 Inhibitor, Topoisomerase,3 Inhibitors, Topoisomerase,I Inhibitor, Topoisomerase,III Inhibitor, Topoisomerase,III Inhibitors, Topoisomerase,Inhibitor, Topoisomerase 1,Inhibitor, Topoisomerase 3,Inhibitor, Topoisomerase I,Inhibitor, Topoisomerase III,Inhibitors, Topoisomerase 1,Inhibitors, Topoisomerase 3,Inhibitors, Topoisomerase I,Inhibitors, Topoisomerase III

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