Autoantibodies define a family of proteins with conserved double-stranded RNA-binding domains as well as DNA binding activity.
Cellular responses to viral infection are signaled by double-stranded (ds) RNA, which is not found in substantial amounts in uninfected cells. Although cellular dsRNA-binding proteins have been described, their characterization is incomplete. We show that dsRNA-binding proteins are prominent autoantigens. Sera from B6 and B10.S mice with pristane-induced lupus and human autoimmune sera immunoprecipitated a novel set of 130-, 110-, 90-, 80-, and 45-kDa proteins. The proteins were all major cellular poly(IC)-binding factors. N-terminal amino acid sequences of p110 and p90 were identical and matched nuclear factor (NF) 90 and M phase phosphoprotein 4. p45 and p90 were identified as the NF45.NF90 complex, which binds the interleukin-2 promoter as well as certain highly structured viral RNAs. NF90.NF45 and M phase phosphoprotein 4 belong to a large group of proteins with conserved dsRNA-binding motifs. Besides binding dsRNA, NF90.NF45, p110, and p130 had single-stranded and dsDNA binding activity. Some sera contained autoantibodies whose binding was inhibited by poly(IC) but not single-stranded DNA or vice versa, suggesting that the DNA- and RNA-binding sites are different. These autoantibodies will be useful probes of the function of dsRNA-binding proteins. Their interaction with dsRNA, an immunological adjuvant, also could promote autoimmunity.
Satoh
M
M
Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7280, USA.
Shaheen
V M
VM
Kao
P N
PN
Okano
T
T
Shaw
M
M
Yoshida
H
H
Richards
H B
HB
Reeves
W H
WH
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism*; D001665:Binding Sites; D002846:Chromatography, Affinity; D004247:DNA / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D020014:K562 Cells; D051379:Mice; D008969:Molecular Sequence Data; D012330:RNA, Double-Stranded / Q000276:immunology / Q000378:metabolism; D012367:RNA, Viral / Q000276:immunology; D016601:RNA-Binding Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013997:Time Factors
D001323:Autoantibodies; D004268:DNA-Binding Proteins; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D004247:DNA