Molecular Genetics of Maternal RNA Regulation in C. elegans

母体RNA的调节对早期发育至关重要。 金布尔博士建议采取基因和分子相结合的方法 分析线虫C. 优雅fem-3和glp-1基因表达母体RNA， 调节性别决定和诱导细胞相互作用， 早期胚胎初步证据显示， 这些RNA的非翻译区调节它们在转录水平的活性。 翻译水平。金布尔博士建议解决 fem-3和glp-1母源RNA的作用机制 以三种方式控制。首先，她会问， 而glp-1母体RNA受调控。本 最后，她将研究它们内源性RNA的分布， 和蛋白质，并评估它们与多聚核糖体的关联。第二、 她将确定调控所需的序列元件。到 为此，她将注射携带野生型的报告RNA， 将来自FEM-3或GLP-1的突变体序列导入种系和测定 它们在卵母细胞和早期胚胎中的翻译能力。第三、 她将开始分析调节母体RNA的因素。到 为此，她将依靠凝胶迁移试验和对mog-1的分析， 变种人了解母体RNA在哺乳动物中是如何调控的， C.秀丽线虫将提供深入了解这种基本控制， 早期发展，也将允许表达特定的 在早期胚胎中被操纵的蛋白质。

The regulation of maternal RNAs is critical to early development. Dr. Kimble proposes to take a combined genetic and molecular approach to analyze maternal RNA controls in the nematode C. elegans. The fem-3 and glp-1 genes express maternal RNAs that regulate sex determination and inductive cell interactions in early embryos. Preliminary evidence suggests that the 3' untranslated regions of these RNAs regulate their activity at the level of translation. Dr. Kimble proposes to address the mechanisms by which the fem-3 and glp-1 maternal RNAs are controlled in three ways. First, she will ask whether the fem-3 and glp-1 maternal RNAs are translationally controlled. To this end, she will examine the distribution of their endogenous RNAs and proteins and assess their association with polysomes. Second, she will identify sequence elements necessary for regulation. To this end, she will inject reporter RNAs carrying wild-type and mutant sequences from fem-3 or glp-1 into the germ line and assay their translational capacity in oocytes and early embryos. Third, she will begin to analyze factors that regulate maternal RNAs. To this end, she will rely on gel shift assays and analysis of mog-1 mutants. An understanding of how maternal RNAs are regulated in C. elegans will provide insight into this fundamental control of early development and also will allow expression of specific proteins to be manipulated in early embryos.