Translational repressor bruno plays multiple roles in development and is widely conserved.
oskar (osk) mRNA is tightly localized to the posterior pole of the Drosophila oocyte, where the subsequent expression of Osk protein directs abdomen and germ-line formation in the developing embryo. Misplaced expression of Osk protein leads to lethal body patterning defects. The Osk message is translationally repressed before and during the localization process, ensuring that Osk protein is only expressed after the mRNA has reached the posterior. An ovarian protein, Bruno (Bru), has been implicated as a translational repressor of osk mRNA. Here we report the isolation of a cDNA encoding Bru using a novel approach to the expression 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 protein and its pattern of accumulation within the oocyte, indicate that Bru regulates multiple mRNAs involved in female and male gametogenesis as well as early in embryogenesis. Genetic experiments provide further 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 belongs to an evolutionarily conserved family of genes, suggesting that Bru-mediated translational regulation may be widespread. Models for the molecular mechanism of Bru function are discussed.
Webster
P J
PJ
Department of Biological Sciences, Stanford University, California 94305-5020, USA.
Liang
L
L
Berg
C A
CA
Lasko
P
P
Macdonald
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics; D053487:DEAD-box RNA Helicases; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins; D019143:Evolution, Molecular; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D017344:Genes, Insect; D019476:Insect Proteins / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009866:Oogenesis / Q000235:genetics; D010641:Phenotype; D014176:Protein Biosynthesis / Q000235:genetics*; D020365:RNA Helicases; D012316:RNA Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D016211:Transforming Growth Factor alpha; D015291:Transforming Growth Factors / Q000235:genetics
D029721:Drosophila Proteins; D019476:Insect Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D016211:Transforming Growth Factor alpha; C093437:bru1 protein, Drosophila; C083730:grk protein, Drosophila; C091675:osk protein, Drosophila; D015291:Transforming Growth Factors; D012316:RNA Nucleotidyltransferases; C088269:vas protein, Drosophila; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases