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 eryth ematosus and Sjogren's syndrome contain antibodies in their sera direc ted against Certain normal cellular components such as the La/SS-B aut oantigen, an RNA-binding protein believed to function as a putative pr ocessor of RNA polymerase III precursor transcripts. We have identifie d 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 ribonu cleoprotein 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 re vealed a single 1,600-nucleotide transcript expressed throughout embry onic, larval, pupal, and adult development. Surprisingly, whole-mount in situ hybridization experiments revealed that D-La transcripts are n ot present in all ovarian tissues. In addition, early expression throu ghout the embryo is followed by a restricted pattern of mesodermal exp ression that is later confined to the visceral mesoderm, gonads, gut, and salivary glands. These results suggest that D-La may play a more s pecialized role during fly development as opposed to a rather general role inferred by its homology to La proteins from other organisms.