The regulation and function of miR-124 in ascidian neural development

基因调控通常是指转录调控的过程，即从基因控制RNA分子的生产，随后是蛋白质的生产。最近，一类被称为microRNAs的小RNA被证明通过一种不同的机制来调节基因的表达。在动物中，microRNAs主要通过抑制RNAs中蛋白质的产生来控制基因活动。由于一个microRNA可能调节数百个基因，它们被认为在生物体的发育中发挥着重要作用。在这个项目中，一种与人类关系密切的简单动物海鞘将被用来研究一种名为miR-124的特定microRNA的调节和功能，它在动物的神经系统中表达。虽然人们对microRNA的功能了解很多，但以前的研究主要使用的是在生物体组织内从正常环境中移除的培养细胞。相比之下，海鞘动物提供了一个很好的整体动物环境，在这个环境中可以识别和表征受这种微小RNA调控的基因。这项建议将使用综合实验方法，结合生物信息学、分子遗传学和经典胚胎学方法来研究miR-124的功能。由于这些研究将使用完全动物的方法进行，预计将发现许多新的miR-124靶点(即在培养细胞实验中遗漏的那些靶点)。此外，该项目将研究miR-124介导的基因调控机制是否在脊椎动物(如老鼠和人类)出现之前进化，以及海鞘动物和脊椎动物是否共享miR-124靶基因。本项目提供的详细分析将有助于更好地了解microRNA在神经系统发育过程中的功能，并将建立海鞘作为研究microRNA功能的良好的整体动物模型。这项提议还将为本科生和研究生提供研究机会，因为他们正在培训成为下一代生物研究人员。

Gene regulation typically refers to the process of transcriptional regulation, that is, the controlled production of an RNA molecule, and subsequently a protein, from a gene. Recently a class of small RNAs, called microRNAs, has been shown to regulate gene expression by a different mechanism. In animals, microRNAs control gene activity primarily by repressing the production of proteins from RNAs. Because a single microRNA may regulate hundreds genes, they are thought to play important roles in the development of organisms. In this project, a simple animal, the ascidian, which is closely related to humans, will be used to study the regulation and function of a particular microRNA, called miR-124, which is expressed in the nervous system of animals. Although much is known about microRNA function, previous studies have primarily used cultured cells that have been removed from their normal environment within the tissues of an organism. In contrast, ascidians provide an excellent whole animal environment in which to identify and characterize the genes regulated by this microRNA. This proposal will use an integrated experimental approach employing bioinformatics, molecular genetics and classical embryological methods to investigate miR-124 function. Because these studies will be done using a whole animal approach, it is expected that many novel miR-124 targets will be found (i.e., ones that have been missed in experiments with cultured cells). In addition, this project will examine whether miR-124 mediated gene regulatory mechanisms evolved prior to the appearance of vertebrates (such as mice and humans) and whether ascidians and vertebrates share miR-124 target genes. The detailed analysis provided by this project will lead to a better understanding of microRNA function during nervous system development and will establish the ascidian as an excellent whole animal model for studying microRNA function. This proposal will also provide research opportunities for both undergraduate and graduate students as they train to become the next generation of biological researchers.