Drosophila Brain Tumor is a translational repressor.
The Drosophila brain tumor (brat) gene encodes a member of the conserved NHL family of proteins, which appear to regulate differentiation and growth in a variety of organisms. One of the founding family members, Caenorhabditis elegans LIN-41, is thought to control posttranscriptional gene expression. However, the mechanism by which LIN-41, or any other NHL protein, acts has not been clear. Using a yeast "four-hybrid" interaction assay, we show that Brain Tumor is recruited to hunchback (hb) mRNA through interactions with Nanos and Pumilio, which bind to the RNA to repress its translation. Interaction with the Nanos/Pumilio/RNA complex is mediated by the Brat NHL domain; single amino acid substitutions in this domain compromise quaternary complex assembly in vitro and hb regulation in vivo. Thus, recruitment of Brat is necessary for translational repression and the normal development of posterior embryonic pattern. In addition to regulating abdominal segmentation, previous genetic analysis has shown that Brat, Nanos, and Pumilio govern 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 suggest that NHL domain proteins are recruited to various mRNAs by combinatorial protein-protein interactions.
Howard Hughes Medical Institute, Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
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Sonoda
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Wharton
D000818:Animals; D003433:Crosses, Genetic; D019926:Cyclin B / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D014921:Wings, Animal / Q000196:embryology
C503698:CycB protein, Drosophila; D019926:Cyclin B; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C412783:brat protein, Drosophila; C061245:hb protein, Drosophila; C074333:pum protein, Drosophila; C070574:nos protein, Drosophila