TRANSLATIONAL REPRESSOR BRUNO PLAYS MULTIPLE ROLES IN DEVELOPMENT ANDIS WIDELY CONSERVED

oskar (osk) mRNA is tightly localized to the posterior pole of the Dro sophila oocyte, where the subsequent expression of Osk protein directs abdomen and germ-line formation in the developing embryo. Misplaced e xpression of Osk protein leads to lethal body patterning defects. The Osk message is translationally repressed before and during the localiz ation process, ensuring that Osk protein is only expressed after the m RNA has reached the posterior. An ovarian protein, Bruno (Bru), has be en implicated as a translational repressor of osk mRNA. Here we report the isolation of a cDNA encoding Bru using a novel approach to the ex pression cloning of an RNA-binding protein, and the identification of previously described mutants in the arrest (aret)-locus as mutants in Bru. The mutant phenotype, along with the binding properties of the pr otein and its pattern of accumulation within the oocyte, indicate that Bru regulates multiple mRNAs involved in female and male gametogenesi s as well as early in embryogenesis. Genetic experiments provide furth er evidence that Bru functions in the translational repression of osk. Intriguingly, we find that Bru interacts physically with Vasa (Vas), an RNA helicase that is a positive regulator of osk translation. Bru b elongs to an evolutionarily conserved family of genes, suggesting that Bru-mediated translational regulation may be widespread. Models for t he molecular mechanism of Bru function are discussed.