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， 在生殖细胞分化过程中协调不同的细胞过程。我们有 大量的初步数据表明，细胞质Rbfox1抑制了 在其3'端含有（U）GCAUG元件的特定靶mRNA的翻译 生殖细胞包囊分化的特定阶段的UTR。通过这项提案，我们 试图描述细胞质Rbfox1调节的详细机制， 生殖细胞囊肿发育过程中阶段特异性mRNA翻译程序。我们 一般的策略是（1）确定什么机制控制独特的蛋白质 Rbfox1在生殖细胞包囊中期的表达模式 分化，减数分裂开始之前，（2）表征Rbfox 1如何分子 调节mRNA靶点的翻译，以实现阶段特异性翻译， 抑制和（3）表征Rbfox1如何调节特定的mRNA， 生殖细胞发育的步骤，如pumilio和性致死，并确定 这些靶点的异位表达在多大程度上有助于Rbfox1突变 表型我们预计，这些努力将提供关键的见解， 翻译控制层次，促进生殖细胞的发展， 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.