RNA-binding proteins in mosquito development

摘要 蚊子在世界范围内传播多种对健康具有重大意义的疾病， 从根本上了解蚊子生殖生物学的研究至关重要 对这些致命疾病媒介的人口控制努力。RNA结合蛋白 （RBP）在模式昆虫系统的早期发育中起核心作用， 已知RBPs在蚊子繁殖中的功能， 与昆虫模型相结合。在这项研究中，我们将解决这一知识差距 使用生物信息学、遗传学和分子生物学方法的组合。在 根据初步数据，综合生物信息学分析确定了一组集中的限制性商业惯例 在蚊子卵母细胞和胚胎发育中具有候选作用。我们将调查 通过使用RNA干扰和CRISPR/Cas9， 标签敲入系，并将采用尖端的分子分析方法， 综合分析，以评估相关RBP对mRNA生命周期的影响。 研究RBP在蚊子繁殖中的功能是非常重要的，因为它将 为基因驱动工作确定新的有吸引力的靶点。此外，由于我们 对转录后基因调控的理解落后于转录调控， 控制在大多数系统中，蚊子生物学的这一新的和基本上未经研究的方面将 （b）增进我们对限制性商业惯例在发展中的作用和机制的一般性了解。

ABSTRACT Mosquitoes transmit multiple diseases of enormous health importance worldwide, and research to fundamentally understand the reproductive biology of mosquitoes is critical to population control efforts for these deadly disease vectors. While RNA-binding proteins (RBPs) play central roles in early development in model insect systems, very little is known about the function of RBPs in mosquito reproduction, and significant differences with the insect models are expected. In this study, we will address this knowledge gap using a combination of bioinformatic, genetic and molecular biology approaches. In preliminary data, integrative bioinformatic analysis has identified a focused set of RBPs with candidate roles in mosquito oocyte and embryo development. We will investigate their function in Aedes aegypti through the use of RNA interference and CRISPR/Cas9 tag knock-in lines, and will employ cutting-edge molecular profiling methods and integrative analysis to assess the impact of relevant RBPs on the mRNA lifecycles. Investigating RBP function in mosquito reproduction is highly significant because it would identify novel attractive targets for gene drive efforts. Additionally, since our understanding of post-transcriptional gene regulation lags behind that of transcriptional control in most systems, this novel and largely unstudied aspect of mosquito biology will advance our general knowledge of the roles and mechanisms of RBPs in development.