Genetic analysis of a La homolog in Drosophila melanogaster

People afflicted with certain rheumatological autoimmune diseases produce a utoantibodies directed against a select group of proteins such as the La au toantigen. Biochemical studies Rave revealed La to be a promiscuous RNA-bin ding protein that appears to play a role in a variety of intracellular acti vities such as processing and/or transport of RNA polymerase III precursor transcripts and translational regulation from internal ribosome entry sites (IRES). We have previously identified an RNA-binding protein that is a Dro sophila melanogaster homolog of La (D-La) and shown that early transcript a ccumulation throughout the embryo is later refined to be most prevalent in the visceral mesoderm, gut, gonads and salivary glands. Here we report the first in vivo genetic characterization of a La homolog in a multicellular e ukaryote. Lethality was observed in homozygous larvae harboring a small chr omosomal deletion that removed the D-La gene, which was rescued by an induc ible D-La cDNA transgene. This implies that D-La confers essential function s for larval development, In addition, loss of D-La function gives rise to defects in embryonic midgut morphogenesis; one of the midgut defects correl ates with loss of Ultrabithorax (Ubx) expression along the second midgut co nstriction.Finally, genetic interactions between chromosomal deficiencies t hat remove D-La and certain Ubx alleles were demonstrated in adults. Our re sults support the hypothesis that D-La provides essential functions for pro per Drosophila development and imply that the conserved La family of protei ns may perform critical developmental Functions in higher eukaryotes.