RNA polymerase II precursor mrna (hnrna) introns introns U1RNP. splicing
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1 DNA RNA polymerase II precursor mrna (hnrna) introns introns U2RNP splicing mrna U1RNP U5RNP U4/U6RNP splicing The genetic information of DNA is transcribed to precursor mrna (heterogeneous nuclear RNA, hnrna). The small nuclear RNAs (small nuclear RNA, snrna) such as U1, U2, U4/U6 and U5 RNA are involved in the splicing of hnrna. These RNAs are complexed with proteins to form ribonucleoproteins (RNPs). Anti-U1RNP antibody U1 RNA Sm B B' D E F G C A RNP photo21 ignificance Coarse speckled (larger granular) nuclear pattern with no nucleolar and cytoplasmic staining. The chromosomal regions do not stain in mitotic cells. 3 kinds of polypeptides bound to U1 RNA; U1RNP-68kD, U1RNP-A(34kD), U1RNP-C(23kD) DID, ELISA, WB, Immunoprecipitation, CLEIA The presence of the antibodies to U1RNP constitute one of major diagnostic criteria for MCTD. References 15, 16 14
2 Anti-Sm antibody photo 22 AF/CDC-5* Coarse speckled staining similar to those of anti-u1rnp antibody. U1, U2, U4/U6 and U5 RNA-bound proteins with 5 kinds of epitopes, B'/B(29kD/28kD), D(16kD), E(12kD), F(11kD) and G(10kD). The main epitopes comprise B'/B and D polypeptides. Antibodies to E-F-G complex as dominant epitopes are also reported. DID, ELISA, WB, Immunoprecipitation, CLEIA Marker antibody for SLE. The presence of anti-sm antibody is included in the criteria for the classification of SLE by the American College of Rheumatology. References 17 Anti-U2RNP antibody / Anti-U1U2RNP antibody Coarse speckled nuclear staining similar to those of anti-u1rnp antibody. U2RNA-bound proteins with 2 kinds of epitopes on A'(32kD) and B"(28.5kD). Immunoprecipitation Polymyositis/scleroderma overlap syndrome References 3, 15, 16 photo 23 SLE: systemic lupus erythematosus, SSc: systemic sclerosis, MCTD: mixed connective tissue disease, SS: Sjögren's syndrome, PM/DM: polymyositis/dermatomyositis, RA: rheumatoid arthritis, PBC: primary biliary cirrhosis, AIH: autoimmune hepatitis 15
3 Anti-hnRNP antibody photo 24 Large speckled (granular) nucleoplasmic staining with no chromosomal fluorescence in mitotic cells. The antibodies frequently coexist with anti-u1rnp and anti-sm antibodies, and give coarse speckled patterns. hnrna bound proteins-a/b, A1, A2, C, I ELISA, WB These antibodies were first reported in patients with MCTD. Antibodies to the A/ B polypeptides and those to the A1 and A2 polypeptides occur in SLE and rheumatoid arthritis, respectively. Recently, antihnrnp-i antibodies with weak nuclear staining specific for scleroderma and antihnrnp-c antibodies with speckled nuclear staining in scleroderma were reported. References 18, 19, 20, 21 Anti-SS-A/Ro antibody Y-RNA Ro 60 kd Ro 52 kd SS-A/Ro SS-B/La La photo 2 F/CDC-7* Fine speckled nuclear staining observed in acetone-fixed slides, but not in alcohol-fixed ones. The chromosomal region shows no fluorescence in mitotic cells. Y1-Y5RNA-bound proteins (52kD, 60kD) DID, ELISA, WB, Immunoprecipitation, CLEIA These antibodies occur most frequently in patients with SS, and those with SLE. Sometimes found in patients with rheumatoid arthritis, myositis or scleroderma. The presence of the antibodies in the mother is associated with neonatal lupus and congenital heart block. The presence of anti-ss-a antibodies constitutes one of the diagnostic criterion of SS in Europe. References 22 16
4 Anti-SS-B/La antibody photo 26 AF/CDC-2* Fine dense speckled nuclear staining is observed in interphase cells with no chromosomal fluorescence in mitotic cells. 48 kd SS-B/La protein, a termination factor for RNA polymerase III transcription DID, ELISA, WB, Immunoprecipitation, CLEIA The antibodies are found in patients with SS and SLE. As with anti-ss-a antibodies, the presence of these antibodies is associated with neonatal lupus and congenital heart block. The antibodies were reported to be frequently positive in patients with recurrent annular erythema. The presence of anti- SS-B antibodies constitutes one of the diagnostic criterion of SS in Europe. References 23 Anti-p80 coilin antibody Granular or few nuclear dots staining**, 0 to 6 dots (ave. 2 dots) per nucleus fluorescence. The distinct large dotty fluorescence can be seen in cells during S and G2 phases, and mitotic cells show no staining. photo 27 p80 coilin, the 80kD protein composing the coiled body in nucleoplasm. WB These antibodies occur in some patients with SS and those with primary biliary cirrhosis. References 24, 25 SLE: systemic lupus erythematosus, SSc: systemic sclerosis, MCTD: mixed connective tissue disease, SS: Sjögren's syndrome, PM/DM: polymyositis/dermatomyositis, RA: rheumatoid arthritis, PBC: primary biliary cirrhosis, AIH: autoimmune hepatitis 17
5 Anti-Sp100 antibodies photo 28 Granular or multiple (1 to 24) nuclear dots staining**. Sp100 protein. Multiple nuclear dots staining is also observed by the antibodies to promyelocytic leukemia (PML) protein, NDP53 (a binding protein to PML oncogenic domain including Sp100). WB These antibodies occur in some patients with PBC. References 26, 27, 28 ** Since the numbers of staining dots seen in few nuclear dots and multiple nuclear dots patterns overlap each other, it is sometimes difficult to distinguish these patterns. These patterns are often called granular or nuclear dots patterns. 18
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