New mechanisms and technologies for understanding post-transcriptional gene regulation in neurons

我们研究计划的总体目标是了解神经元 建立突触可塑性和回路所需的蛋白质合成的精确空间和模式 队形。这种调控很大程度上发生在RNA水平上，我的实验室专注于发现新的 能够实现这种基于RNA的控制的调控机制。我们的研究集中在三个项目上：(1) 神经元mRNAs的表观转录调控。我们经常被誉为帮助开创了一个新的领域 RNA生物学称为“表位转录组学”，即信使核糖核酸的命运和功能是由 调节性核苷酸修饰。我实验室的一个主要项目关注的是表位转录调控 通过这些修饰，信使核糖核酸在神经元中的命运。(2)破译RNA引导的表观遗传机制 脆性X综合征中的沉默。我们最近发现脆性X综合征是由CGG引起的疾病 重复RNA。我们发现，这种rna与互补的dna形成杂交体来诱导表观遗传学。 沉默，这构成了一条新的表观遗传途径。我们致力于了解这一新领域 表观遗传学和利用这一途径的知识来开发一种全新的方法来治疗这种主要疾病 神经方面的情况。(3)突触转录组功能的揭示技术。在……里面 为了揭示大脑中RNA调控的新见解，我们开发了新的技术来实现成像 以及对信使核糖核酸的分析，也许最著名的是“模拟绿色荧光蛋白的RNA”，包括菠菜。我们要买这些。 荧光适配子达到LIVE中使用的苛刻成像方法所需的下一级别亮度 功能正常的动物。此外，我们将开发新的工程适体，使光控制 突触信使核糖核酸翻译。总体而言，这项研究计划将促进我们对后 神经元中转录基因的调控。

The overall goal of our research program is to understand the intricate mechanisms by which neurons establish the precise spatial and patterns of protein synthesis needed for synaptic plasticity and circuit formation. Much of this regulation occurs at the RNA level, and my laboratory focuses on uncovering novel regulatory mechanisms that enable this RNA-based control. Our research centers around three programs: (1) Epitranscriptomic regulation of neuronal mRNAs. We are often credited with helping to start a new field of RNA biology termed “epitranscriptomics,” the idea that mRNA fate and function is encoded in the RNA by regulatory nucleotide modifications. A major program in my lab focuses on epitranscriptomic regulation of mRNA fate in neurons by these modifications. (2) Deciphering the mechanism of RNA-directed epigenetic silencing in fragile X syndrome. We recently showed that fragile X syndrome is a disease caused by CGG repeat RNA. We found that this RNA forms a hybrid with complementary DNA to induce the epigenetic silencing, which constitutes a new epigenetic pathway. We are committed to understanding this new area of epigenetics and using knowledge of this pathway to develop a completely new approach to treat this major neurological condition. (3) Technologies for revealing the function of the synaptic transcriptome. In order to reveal new insights into RNA regulation in the brain, we develop novel technologies to enable imaging and analysis of mRNA, perhaps most notably “RNA mimics of GFP,” including Spinach. We will take these fluorogenic aptamers to the next level of brightness needed for the demanding imaging approaches used in live functioning animals. Additionally, we will be developing new engineered aptamers that enable light-control of synaptic mRNA translation. Overall, this research program will advance our understanding of post- transcriptional gene regulation in neurons.