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. Althoug h cellular dsRNA-binding proteins have been described, their characterizati on is incomplete. We show that dsRNA-binding proteins are prominent autoant igens. Sera from B6 and B10.S mice with pristane-induced lupus and human au toimmune sera immunoprecipitated a novel set of 130-, 110-, 90-, 80-, and 4 5-kDa proteins. The proteins were all major cellular poly(IC)-binding facto rs. N-terminal amino acid sequences of p110 and p90 were identical and matc hed nuclear factor (NF) 90 and M phase phosphoprotein 4. p45 and p90 were i dentified as the NF45 . NF90 complex, which binds the interleukin-a promote r 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-b inding motifs. Besides binding dsRNA, NF90 . NF45, p110, and p130 had singl e-stranded and dsDNA binding activity. Some sera contained autoantibodies w hose 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 prote ins. Their interaction with dsRNA, an immunological adjuvant, also could pr omote autoimmunity.