DAZ GENES AND RNA BINDING IN HUMAN GERM CELL DEVELOPMENT

除了它是如何受激素调节之外，我们对人类生殖细胞在分子水平上的发育知之甚少。然而，生殖细胞发育经常出现异常，导致全球10%-15%的夫妇患上几种常见的肿瘤和不孕不育。我建议这项研究的总体目标是更好地了解人类生殖的遗传机制，特别是生殖细胞在早期胚胎中是如何分配和/或维持的。我研究这一过程的方法是探索DAZ(在无精子症中缺失)蛋白家族及其核糖核酸靶点(S)在生殖细胞早期发育中的作用，因为许多证据表明这些蛋白质在生殖细胞早期分配和/或维持中发挥作用。我将确定什么RNA分子与DAZ蛋白相互作用，以及DAZ通过什么机制(例如，转录激活、翻译抑制或细胞周期调节)确保生殖细胞种群的分配或维持。具体地说，我的目标是：1.鉴定DAZ蛋白结合的RNA底物。2.对编码DAZ家族蛋白底物S的基因(S)进行了特征分析。3.在不育男性中筛查突变并确定与核糖核酸底物突变相关的表型(S)。

Apart from how it is regulated by hormones, we know little about germ cell development in humans at a molecular level. Yet germ cell development is frequently aberrant, causing several common tumors and infertility in 10-15 percent couples worldwide. The overall goal of the research I propose is to gain a greater understanding of the genetic mechanisms of human reproduction, especially how germ cells are allocated and/or maintained in the early embryo. My approach to investigate this process is to explore the role of the DAZ (Deleted in AZoospermia) family of proteins and their RNA target(s) in early germ cell development since much evidence suggests these proteins function in early germ cell allocation and/or maintenance. I will determine what RNA molecules interact with DAZ protein and by what mechanism (for example, transcriptional activation, translational repression, or modulation of the cell cycle) DAZ assures that allocation or maintenance of germ cell populations occurs. Specifically, my aims are to: 1. Identify the RNA substrates to which the DAZ proteins bind. 2. Characterize the gene(s) encoding the RNA substrate(s) for DAZ family proteins. 3. Screen for mutations in infertile men and determine the phenotypes associated with mutations of the RNA substrate(s).