title: Patterning of the Drosophila oocyte by a sequential translation repression program involving the d4EHP and Belle translational repressors.
abstract: During Drosophila development, translational control plays a crucial role in regulating gene expression, and is particularly important during pre-patterning of the maturing oocyte. A critical step in translation initiation is the binding of the eukaryotic translation initiation factor 4E (eIF4E) to the mRNA cap structure, which ultimately leads to recruitment of the ribosome. d4EHP is a translational repressor that prevents translation initiation by out-competing eIF4E on the cap structure for a subset of mRNAs. However, only two examples of mRNAs subject to d4EHP translation repression in Drosophila are known. Here we show that the belle (bel) mRNA is translationally repressed by the d4EHP protein in the Drosophila ovary. Consistent with this regulation, d4EHP overexpression in the ovary phenocopies the bel mutant. We also provide evidence that the Bel protein binds to eIF4E and may itself function as a translation repressor protein, with bruno as a potential target for Bel repression in the oocyte. Bruno is known to repress the mRNA of the key oocyte axis determinant oskar (osk) during oogenesis, and we find that an increase in the level of Bruno protein in bel mutant ovaries is associated with a reduction in Osk protein. Overall, our data suggest that a translational regulatory network exists in which consecutive translational repression events act to correctly pattern the Drosophila oocyte.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Yarunin
authors.forename: Robin E
authors.initials: RE
authors.lastname: Harris
authors.forename: Mark P
authors.initials: MP
authors.lastname: Ashe
authors.forename: Hilary L
authors.initials: HL
authors.lastname: Ashe
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D009865:Oocytes / Q000502:physiology*; D009866:Oogenesis / Q000235:genetics; D011485:Protein Binding; D014176:Protein Biosynthesis / Q000235:genetics; D012315:RNA Caps / Q000378:metabolism; D020365:RNA Helicases / Q000096:biosynthesis / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; D012315:RNA Caps; D016601:RNA-Binding Proteins; C093437:bru1 protein, Drosophila; C504669:eIF4EHP protein, Drosophila; C091675:osk protein, Drosophila; C558829:Bel protein, Drosophila; D020365:RNA Helicases