Regulation of mRNA translation during germline cyst differentiation

项目摘要 转录后基因调控已经成为一种关键的控制机制， 在生殖细胞分化期间协调不同的细胞过程。我们有 大量初步数据表明，细胞质RBFOX1抑制了 翻译在其3‘端包含(U)个GCAUG元件的特定靶RNA 胚系孢子分化特定阶段的UTRs。通过这项提议，我们 寻求表征细胞质RBFOX1调节的详细机制 生殖细胞囊发育过程中特定阶段的信使核糖核酸翻译程序。我们的 一般的策略是(1)确定控制独特蛋白质的机制 RBFOX1在生殖系包囊中期的表达模式 分化，在减数分裂开始之前，(2)表征RBFOX1如何分子 调节信使核糖核酸靶标的翻译以实现特定阶段的翻译 抑制和(3)表征RBFOX1如何调控早期统治的特定mRNAs 生殖细胞发育的步骤，如Pumilio和性致死，并决定 这些靶标的异位表达在多大程度上促进了RBFOX1突变 表型。我们预计，这些努力将为 促进生殖细胞发育的翻译控制层级 物种。

Project Summary Post-transcriptional gene regulation has emerged as a critical control mechanism that orchestrates diverse cellular processes during germ cell differentiation. We have extensive preliminary data that demonstrate cytoplasmic Rbfox1 represses the translation of specific target mRNAs that contain (U)GCAUG elements within their 3' UTRs during specific stages of germline cyst differentiation. Through this proposal, we seek to characterize the detailed mechanisms by which cytoplasmic Rbfox1 regulates stage specific mRNA translation programs during germ cell cyst development. Our general strategy is to (1) determine what mechanisms control the unique protein expression pattern of Rbfox1 during the intermediate stages of germline cyst differentiation, prior to the onset of meiosis, (2) characterize how Rbfox1 molecularly regulates the translation of mRNA targets to achieve stage-specific translational repression and (3) characterize how Rbfox1 regulates specific mRNAs that govern early steps of germ cell development, such as pumilio and sex-lethal, and determine the extent to which ectopic expression of these targets contributes to Rbfox1 mutant phenotypes. We anticipate that these efforts will provide key insights into the translational control hierarchies that promote the development of germ cells across species.