Characterization of DNA binding properties and sequence specificity of the human 52 kDa Ro/SS-A (Ro52) zinc finger protein.
The Ro52 protein is an autoantigen in Sjögren's Syndrome and systemic lupus erythematosus. Although its function is not yet known, sequence similarities to other proteins suggest that it binds to DNA. In this study, the hypothesis that Ro52 recognizes particular nucleic acid sequences was tested. Ro52 bound to double stranded but not single stranded DNA. 1,10-Phenanthroline, a chelater of zinc, was found to inhibit this interaction, suggesting that the zinc fingers of Ro52 are functional. DNA sequences were selected from an oligonucleotide library by binding to Ro52 followed by amplification by Taq DNA polymerase in order to characterize the DNA sequence-binding motif for this protein. These studies support the hypothesis that Ro52 is functionally a member of a family of zinc finger proteins, many of which are known to bind to DNA or regulate gene expression. We speculate that Ro52 functions as a transcription factor, and that its disregulation may have important consequences in the expression or susceptibility of certain autoimmune diseases.
Frank
M B
MB
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, 73104, USA. frank@omrf.ouhsc.edu
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D004586:Electrophoresis; D006801:Humans; D008969:Molecular Sequence Data; D010618:Phenanthrolines / Q000494:pharmacology*; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D016335:Zinc Fingers; D000099207:SS-A Antigen
D001324:Autoantigens; D004268:DNA-Binding Proteins; D010618:Phenanthrolines; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C116006:RO60 protein, human