RNA-binding proteins in mosquito development

蚊子发育过程中的 RNA 结合蛋白

• 批准号: 10362575
• 负责人: FEDOR V KARGINOV
• 金额: $ 22.66万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-02 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10362575
• 关键词: Address; Aedes; Binding; Bioinformatics; Biology; Blood; CRISPR/Cas technology; Candidate Disease Gene; Culicidae; Data; Deposition; Development; Developmental Biology; Disease; Disease Vectors; Embryonic Development; Event; Female; Fertility; Foundations; Gene Expression; Gene Proteins; Genes; Genetic; Genomics; Growth and Development function; Health; Insecta; Intervention; Knock-in; Knowledge; Messenger RNA; Methods; Modeling; Molecular; Molecular Biology; Molecular Profiling; Oocytes; Physiology; Play; Population; Population Control; Positioning Attribute; Post-Transcriptional Regulation; Proteins; RNA; RNA Interference; RNA-Binding Proteins; RNA-Protein Interaction; Reagent; Regulation; Reproduction; Reproductive Biology; Research; Role; Specificity; Sterility; System; Target Populations; Tissues; Transcriptional Regulation; Translations; feeding; fitness; human disease; mosquito reproduction; novel; protein function; reproductive; sex; tool; transcriptomics; vector

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.

摘要 蚊子在全世界传播多种对健康具有巨大重要性的疾病，以及 从根本上了解蚊子繁殖生物学的研究是至关重要的 对这些致命疾病媒介的人口控制努力。而RNA结合蛋白 限制性商业惯例(RBPs)在模式昆虫系统的早期发育中发挥核心作用，但很少起作用 了解限制性商业惯例在蚊子繁殖中的作用，并有显著差异 预计将会有昆虫模型。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……里面 初步数据，综合生物信息学分析确定了一组重点关注的限制性商业惯例 在蚊子卵母细胞和胚胎发育中扮演候选角色。我们会调查的 它们通过RNA干扰和CRISPR/Cas9在埃及伊蚊中的作用 TAG-in-in系列，并将采用尖端的分子图谱方法和 综合分析以评估相关限制性商业惯例对信使核糖核酸生命周期的影响。 研究RBP在蚊子繁殖中的功能具有非常重要的意义，因为它将 为基因驱动努力确定新的有吸引力的目标。另外，由于我们的 对转录后基因调控的理解滞后于转录调控 在大多数系统中，蚊子生物学的这一新颖且基本上未被研究的方面将 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知识。