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J Biol Chem, Vol. 274, Issue 49, 34598-34604, December 3, 1999

Autoantibodies Define a Family of Proteins with Conserved Double-stranded RNA-binding Domains as Well as DNA Binding Activity

Minoru Satoh, Victoria M. Shaheen, Peter N. KaoDagger , Tetsuroh Okano§, Melody Shaw, Hideo Yoshida, Hanno B. Richards, and Westley H. Reeves

From the Department of Medicine and Microbiology and Immunology, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7280, the Dagger  Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California 94305-5236, and the § Laboratory of Clinical Immunology, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, 228 Japan

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.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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