Drosophila brain tumor is a translational repressor

The Drosophila brain tumor (brat) gene encodes a member of the conserved NH L family of proteins, which appear to regulate differentiation and growth i n a variety of organisms. One of the founding family members, Caenorhabditi s elegans LIN-41, is thought to control posttranscriptional gene expression . However, the mechanism by which LIN-41, or any other NHL protein, acts ha s not been clear. Using a yeast "four-hybrid" interaction assay, we show th at Brain Tumor is recruited to hunchback (hb) mRNA through interactions wit h Nanos and Pumilio, which bind to the RNA to repress its translation. Inte raction with the Nanos/Pumilio/ RNA complex is mediated by the Brat NHL dom ain; single amino acid substitutions in this domain compromise quaternary c omplex assembly in vitro and hb regulation in vivo. Thus, recruitment of Br at is necessary for translational repression and the normal development of posterior embryonic pattern. In addition to regulating abdominal segmentati on, previous genetic analysis has shown that Brat, Nanos, and Pumilio gover n a variety of developmental processes. We examined the role of Brat in two of these processes-regulation of maternal Cyclin B mRNA in the embryo and regulation of imaginal disc development. The results of these experiments s uggest that NHL domain proteins are recruited to various mRNAs by combinato rial protein-protein interactions.