Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus.
Journal: 1980/March - Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
PUBMED: 316537
Abstract:
Patients with systemic lupus erythematosus often possess antibodies against two nuclear antigens called Sm and RNP (ribonucleoprotein). We have established the molecular identity of these antigens by analyzing immune precipitates of nuclear extracts from mouse Ehrlich ascites cells labeled with (32)P and (35)S. Anti-Sm serum selectively precipitates six small nuclear RNA molecules (snRNAs); anti-RNP serum reacts with only two of these; and a third serum, characterized as mostly anti-RNP, precipitates a subset of three snRNA bands. Three of the six RNAs are identified by fingerprint analysis as the previously characterized and highly abundant nucleoplasmic snRNA species U1a (171 nucleotides), U1b, and U2 (196 nucleotides). The other three RNAs (U4, U5, and U6) likewise are uridine rich and contain modified nucleotides, but they are smaller, with lengths of about 145, 120, and 95 residues, respectively. Each of the six snRNAs is complexed with and apparently antigenic by virtue of association with specific proteins. All three sera precipitate an identical complement of seven different polypeptides ranging in molecular weight from 12,000 to 35,000; these proteins are abundant in nuclear extracts, but are neither histones nor the major polypeptides comprising the 30S heterogeneous nuclear RNP particles of mammalian nuclei. Our data argue that each of the six snRNAs exists in a separate small nuclear ribonucleoprotein (snRNP) complex with a total molecular weight of about 175,000. We find that human antisera also precipitate snRNAs from a wide range of vertebrate species and from arthropods. We discuss the antigenic snRNPs in relation to the published literature on snRNAs and nuclear RNPs and consider possible functions of snRNPs in nuclear processes.
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Proc Natl Acad Sci U S A 76(11): 5495-5499

Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus

Abstract

Patients with systemic lupus erythematosus often possess antibodies against two nuclear antigens called Sm and RNP (ribonucleoprotein). We have established the molecular identity of these antigens by analyzing immune precipitates of nuclear extracts from mouse Ehrlich ascites cells labeled with P and S. Anti-Sm serum selectively precipitates six small nuclear RNA molecules (snRNAs); anti-RNP serum reacts with only two of these; and a third serum, characterized as mostly anti-RNP, precipitates a subset of three snRNA bands. Three of the six RNAs are identified by fingerprint analysis as the previously characterized and highly abundant nucleoplasmic snRNA species U1a (171 nucleotides), U1b, and U2 (196 nucleotides). The other three RNAs (U4, U5, and U6) likewise are uridine rich and contain modified nucleotides, but they are smaller, with lengths of about 145, 120, and 95 residues, respectively. Each of the six snRNAs is complexed with and apparently antigenic by virtue of association with specific proteins. All three sera precipitate an identical complement of seven different polypeptides ranging in molecular weight from 12,000 to 35,000; these proteins are abundant in nuclear extracts, but are neither histones nor the major polypeptides comprising the 30S heterogeneous nuclear RNP particles of mammalian nuclei. Our data argue that each of the six snRNAs exists in a separate small nuclear ribonucleoprotein (snRNP) complex with a total molecular weight of about 175,000. We find that human antisera also precipitate snRNAs from a wide range of vertebrate species and from arthropods. We discuss the antigenic snRNPs in relation to the published literature on snRNAs and nuclear RNPs and consider possible functions of snRNPs in nuclear processes.

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  • Notman DD, Kurata N, Tan EM. Profiles of antinuclear antibodies in systemic rheumatic diseases. Ann Intern Med. 1975 Oct;83(4):464–469. [PubMed] [Google Scholar]
  • Provost TT. Subsets in systemic lupus erythematosus. J Invest Dermatol. 1979 Mar;72(3):110–113. [PubMed] [Google Scholar]
  • Mattioli M, Reichlin M. Characterization of a soluble nuclear ribonucleoprotein antigen reactive with SLE sera. J Immunol. 1971 Nov;107(5):1281–1290. [PubMed] [Google Scholar]
  • Tan EM, Kunkel HG. Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus. J Immunol. 1966 Mar;96(3):464–471. [PubMed] [Google Scholar]
  • Mattioli M, Reichlin M. Physical association of two nuclear antigens and mutual occurrence of their antibodies: the relationship of the SM and RNAprotein (MO) systems in SLE sera. J Immunol. 1973 May;110(5):1318–1324. [PubMed] [Google Scholar]
  • Kessler SW. Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A. J Immunol. 1975 Dec;115(6):1617–1624. [PubMed] [Google Scholar]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed] [Google Scholar]
  • Silberklang M, Gillum AM, RajBhandary UL. Use of in vitro 32P labeling in the sequence analysis of nonradioactive tRNAs. Methods Enzymol. 1979;59:58–109. [PubMed] [Google Scholar]
  • Martin T, Billings P, Levey A, Ozarslan S, Quinlan T, Swift H, Urbas L. Some properties of RNA:protein complexes from the nucleus of eukaryotic cells. Cold Spring Harb Symp Quant Biol. 1974;38:921–932. [PubMed] [Google Scholar]
  • Zieve G, Penman S. Small RNA species of the HeLa cell: metabolism and subcellular localization. Cell. 1976 May;8(1):19–31. [PubMed] [Google Scholar]
  • Ro-Choi TS, Redy R, Henning D, Takano T, Taylor CW, Busch H. Nucleotide sequence of 4.5 S ribonucleic acid of Novikoff hepatoma cell nuclei. J Biol Chem. 1972 May 25;247(10):3205–3222. [PubMed] [Google Scholar]
  • Reddy R, Ro-Choi TS, Henning D, Busch H. Primary sequence of U-1 nuclear ribonucleic acid of Novikoff hepatoma ascites cells. J Biol Chem. 1974 Oct 25;249(20):6486–6494. [PubMed] [Google Scholar]
  • Shibata H, Ro-Choi TS, Reddy R, Choi YC, Henning D, Busch H. The primary nucleotide sequence of nuclear U-2 ribonucleic acid. The 5'-terminal portion of the molecule. J Biol Chem. 1975 May 25;250(10):3909–3920. [PubMed] [Google Scholar]
  • Forget BG, Weissman SM. Oligonucleotides produced by digestion of KB cell ribosomal 5 S ribonucleic acid with specific nucleases. J Biol Chem. 1968 Nov 10;243(21):5709–5723. [PubMed] [Google Scholar]
  • Ro-Choi TS, Reddy R, Henning D, Busch H. 5S RNA 3 , a new nucleus-specific 5S RNA. Biochem Biophys Res Commun. 1971 Aug 20;44(4):963–972. [PubMed] [Google Scholar]
  • Jelinek W, Leinwand L. Low molecular weight RNAs hydrogen-bonded to nuclear and cytoplasmic poly(A)-terminated RNA from cultured Chinese hamster ovary cells. Cell. 1978 Sep;15(1):205–214. [PubMed] [Google Scholar]
  • Douvas AS, Stumph WE, Reyes P, Tan EM. Isolation and characterization of nuclear ribonucleoprotein complexes using human anti-nuclear ribonucleoprotein antibodies. J Biol Chem. 1979 May 10;254(9):3608–3616. [PubMed] [Google Scholar]
  • Hellung-Larsen P, Frederiksen S. Occurrence and properties of low molecular weight RNA components from cells at different taxonomic levels. Comp Biochem Physiol B. 1977;58(3):273–281. [PubMed] [Google Scholar]
  • Raj NB, Ro-Choi TS, Busch H. Nuclear ribonucleoprotein complexes containing U1 and U2 RNA. Biochemistry. 1975 Oct 7;14(20):4380–4385. [PubMed] [Google Scholar]
  • Howard EF. Small nuclear RNA molecules in nuclear ribonucleoprotein complexes from mouse erythroleukemia cells. Biochemistry. 1978 Aug 8;17(16):3228–3236. [PubMed] [Google Scholar]
  • Mory Y, Gefter M. RNA synthesis in isolated nuclei: the use of mercurated nucleotides. Nucleic Acids Res. 1978 Oct;5(10):3899–3912.[PMC free article] [PubMed] [Google Scholar]
  • Bolden A, Aucker J, Weissbach A. Synthesis of herpes simplex virus, vaccinia virus, and adenovirus DNA in isolated HeLa cell nuclei. I. Effect of viral-specific antisera and phosphonoacetic acid. J Virol. 1975 Dec;16(6):1584–1592.[PMC free article] [PubMed] [Google Scholar]
  • Stark BC, Kole R, Bowman EJ, Altman S. Ribonuclease P: an enzyme with an essential RNA component. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3717–3721.[PMC free article] [PubMed] [Google Scholar]
  • Catterall JF, O'Malley BW, Robertson MA, Staden R, Tanaka Y, Brownlee GG. Nucleotide sequence homology at 12 intron--exon junctions in the chick ovalbumin gene. Nature. 1978 Oct 12;275(5680):510–513. [PubMed] [Google Scholar]
  • Deimel B, Louis CH, Sekeris CE. The presence of small molecular weight RNAs in nuclear ribonucleoprotein particles carrying HnRNA. FEBS Lett. 1977 Jan 15;73(1):80–84. [PubMed] [Google Scholar]
  • Northemann W, Scheurlen M, Gross V, Heinrich PC. Circular dichroism of ribonucleoprotein complexes from rat liver nuclei. Biochem Biophys Res Commun. 1977 Jun 20;76(4):1130–1137. [PubMed] [Google Scholar]
  • Guimont-Ducamp C, Sri-Widada J, Jeanteur P. Occurrence of small molecular weight RNAs in Hela nuclear ribonucleoprotein particles containing HnRNA. Biochimie. 1977;59(8-9):755–758. [PubMed] [Google Scholar]
  • Karn J, Vidali G, Boffa LC, Allfrey VG. Characterization of the non-histone nuclear proteins associated with rapidly labeled heterogeneous nuclear RNA. J Biol Chem. 1977 Oct 25;252(20):7307–7322. [PubMed] [Google Scholar]
  • Beyer AL, Christensen ME, Walker BW, LeStourgeon WM. Identification and characterization of the packaging proteins of core 40S hnRNP particles. Cell. 1977 May;11(1):127–138. [PubMed] [Google Scholar]
  • Sharp GC, Irvin WS, May CM, Holman HR, McDuffie FC, Hess EV, Schmid FR. Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective-tissue disease, systematic lupus erythematosus and other rheumatic diseases. N Engl J Med. 1976 Nov 18;295(21):1149–1154. [PubMed] [Google Scholar]
  • Reichlin M. Problems in differentiating SLE and mixed connective-tissue disease. N Engl J Med. 1976 Nov 18;295(21):1194–1195. [PubMed] [Google Scholar]
  • Parker MD. Ribonucleoprotein antibodies: frequency and clinical significance in systemic lupus erythematosus, scleroderma, and mixed connective tissue disease. J Lab Clin Med. 1973 Nov;82(5):769–775. [PubMed] [Google Scholar]
  • Pinnas JL, Northway JD, Tan EM. Antinucleolar antibodies in human sera. J Immunol. 1973 Oct;111(4):996–1004. [PubMed] [Google Scholar]
  • Eisenberg RA, Tan EM, Dixon FJ. Presence of anti-Sm reactivity in autoimmune mouse strains. J Exp Med. 1978 Feb 1;147(2):582–587.[PMC free article] [PubMed] [Google Scholar]
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06510
Abstract
Patients with systemic lupus erythematosus often possess antibodies against two nuclear antigens called Sm and RNP (ribonucleoprotein). We have established the molecular identity of these antigens by analyzing immune precipitates of nuclear extracts from mouse Ehrlich ascites cells labeled with P and S. Anti-Sm serum selectively precipitates six small nuclear RNA molecules (snRNAs); anti-RNP serum reacts with only two of these; and a third serum, characterized as mostly anti-RNP, precipitates a subset of three snRNA bands. Three of the six RNAs are identified by fingerprint analysis as the previously characterized and highly abundant nucleoplasmic snRNA species U1a (171 nucleotides), U1b, and U2 (196 nucleotides). The other three RNAs (U4, U5, and U6) likewise are uridine rich and contain modified nucleotides, but they are smaller, with lengths of about 145, 120, and 95 residues, respectively. Each of the six snRNAs is complexed with and apparently antigenic by virtue of association with specific proteins. All three sera precipitate an identical complement of seven different polypeptides ranging in molecular weight from 12,000 to 35,000; these proteins are abundant in nuclear extracts, but are neither histones nor the major polypeptides comprising the 30S heterogeneous nuclear RNP particles of mammalian nuclei. Our data argue that each of the six snRNAs exists in a separate small nuclear ribonucleoprotein (snRNP) complex with a total molecular weight of about 175,000. We find that human antisera also precipitate snRNAs from a wide range of vertebrate species and from arthropods. We discuss the antigenic snRNPs in relation to the published literature on snRNAs and nuclear RNPs and consider possible functions of snRNPs in nuclear processes.
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