Developmental characterization of a Drosophila RNA-binding protein homologous to the human systemic lupus erythematosus-associated La/SS-B autoantigen.
Patients with humoral autoimmune diseases such as systemic lupus erythematosus and Sjögren's syndrome contain antibodies in their sera directed against certain normal cellular components such as the La/SS-B autoantigen, an RNA-binding protein believed to function as a putative processor of RNA polymerase III precursor transcripts. We have identified cDNA clones from the fruit fly Drosophila melanogaster that encode a protein displaying significant sequence homology with human La/SS-B. The fly protein (which we refer to as D-La) contains a putative ribonucleoprotein 1 (RNP1) and RNP2 RNA-binding domain. D-La also possesses a leucine zipper motif, suggesting that it may interact with itself or other proteins. Using gel retardation analysis, we show that D-La can bind RNA; in addition, we demonstrate the first reported DNA-binding activity associated with a La protein. Northern (RNA) blot analysis revealed a single 1,600-nucleotide transcript expressed throughout embryonic, larval, pupal, and adult development. Surprisingly, whole-mount in situ hybridization experiments revealed that D-La transcripts are not present in all ovarian tissues. In addition, early expression throughout the embryo is followed by a restricted pattern of mesodermal expression that is later confined to the visceral mesoderm, gonads, gut, and salivary glands. These results suggest that D-La may play a more specialized role during fly development as opposed to a rather general role inferred by its homology to La proteins from other organisms.
Public Health Research Institute, New York, New York 10016.
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D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004331:Drosophila melanogaster / Q000196:embryology*; D016350:Leucine Zippers; D008180:Lupus Erythematosus, Systemic; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000097585:SS-B Antigen
D001324:Autoantigens; D018076:DNA, Complementary; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000097585:SS-B Antigen