A human autoantibody specific for a unique conserved region of 28 S ribosomal RNA inhibits the interaction of elongation factors 1 alpha and 2 with ribosomes.
An autoantibody reactive with a conserved sequence of 28 S rRNA (anti-28 S) was identified in serum from a patient with systemic lupus erythematosus. Anti-28 S protected a unique 59-nucleotide fragment synthesized in vitro against RNase T1 digestion. RNA sequence analysis revealed that it corresponded to residues 1944-2002 in human 28 S rRNA and 1767-1825 in mouse 28 S rRNA. These sequences are identical and highly conserved throughout all known eukaryotic 28 S rRNAs. In addition, this fragment is homologous to residues 1052-1110 of Escherichia coli 23 S rRNA that lies within the GTP hydrolysis center of the 50 S ribosomal subunit. Anti-28 S and its Fab fragments strongly inhibited poly(U)-directed polyphenylalanine synthesis, but had no effect on ribosomal peptidyltransferase activity. This effect resulted from inhibition of the binding of elongation factors EF-1 alpha and EF-2 to ribosomes and of the associated GTP hydrolysis. The inhibitory effect was almost completely suppressed by preincubation of anti-28 S with 28 S rRNA or in vitro synthesized RNA fragments containing the immunoreactive region. These results show that the immunoreactive conserved region of 28 S rRNA participates in the interaction of ribosomes with the two elongation factors in protein synthesis.
Uchiumi
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Department of Biochemistry, Niigata University School of Medicine, Japan.
Traut
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Elkon
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Kominami
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D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001483:Base Sequence; D006367:HeLa Cells; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010452:Peptide Biosynthesis; D020648:Peptide Elongation Factor 1; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors / Q000378:metabolism*; D010455:Peptides; D011233:Precipitin Tests; D012339:RNA, Ribosomal, 28S / Q000276:immunology* / Q000378:metabolism; D015183:Restriction Mapping; D012270:Ribosomes / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid
D001323:Autoantibodies; D020648:Peptide Elongation Factor 1; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors; D010455:Peptides; D012339:RNA, Ribosomal, 28S; C012001:polyphenylalanine