The Mechanism and Significance of Evf ncRNA regulation of the Dix genes

这个项目有两个主要目标。在第一，我们希望获得更好的 理解一种新的RNA降解转录调控机制。第二，我们希望更好地了解GABA能神经元的分化和迁移是如何被控制的。 第一个目标集中在新的非编码RNA，胚胎腹前脑(EVF)，如何影响DLX 5/6增强子的转录。EVF ncRNAs是第一个被发现的影响同源结构域蛋白转录活性的发育调节ncRNAs。EVF ncRNAs也是第一个与含有同源异型盒的转录因子相互作用和复合的ncRNAs。因此，这项拟议的研究将是第一次调查发育调节的ncRNA依赖的增强子活性调节在体内的作用。从被认为与不同疾病有关的调控RNA的数量来看，从机制上研究RNA功能的重要性是显而易见的。这些包括：Prader Willi综合征，DiGeorge综合征，Beckwith-Wiedeman综合征，脊髓小脑性共济失调8型，以及 脐带状发育不良。

There are two main goals of this project. In the first, we hope to gain a better understanding of a novel mechansim of RNA depednent transcriptional regulation. In the second, we hope to gain a better understanding of how GABAergic neuronal differentiation and migration are comtrolled. The first goal focuses on how the novel non-coding RNAs, embryonic ventral forebrain (Evf), influence transcription of the Dlx 5/6 enhancer. Evf ncRNAs are the first developmentally regulated ncRNAs to be discovered that affect the transcriptional activity of a homeodomain protein. Evf ncRNAs are also the first ncRNAs shown to cooperate and complex with a homeobox-containing transcription factor. The proposed studies would therefore be the first to investigate the in vivo role of developmentally regulated ncRNA-dependent modulation of enhancer activity. The importance of mechanistic studies of RNA function is clear from the number of regulatory RNAs thought to be involved different diseases. These include: Prader Willi Syndrome, diGeorge Syndrome, Beckwith-Wiedeman syndrome, Spinocerebellar ataxia type 8, and campomelic dysplasia.