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

了解神经元转录后基因调控的新机制和新技术

基本信息

批准号：
10626129
负责人：
SAMIE R JAFFREY
金额：
$ 108.48万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2027-05-31
项目状态：
未结题

项目摘要

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.

我们研究计划的总体目标是了解神经元的复杂机制建立突触可塑性和电路所需的蛋白质合成的精确空间和模式这种调控大部分发生在 RNA 水平，我的实验室致力于发现新的机制。我们的研究中心围绕三个项目：(1) 神经元 mRNA 的表观转录组调控经常被认为有助于开创一个新的领域。 RNA 生物学称为“表观转录组学”，即 mRNA 的命运和功能由 RNA 编码我实验室的一个主要项目集中于表观转录组调控。 (2) 破译RNA介导的表观遗传机制脆性 X 综合征的沉默我们最近表明，脆性 X 综合征是一种由 CGG 引起的疾病。我们发现这种 RNA 与互补 DNA 形成杂交体以诱导表观遗传。沉默，构成了一个新的表观遗传途径，我们致力于了解这一新领域。表观遗传学并利用该途径的知识开发一种全新的方法来治疗该疾病 (3) 揭示突触转录组功能的技术。为了揭示大脑中 RNA 调节的新见解，我们开发了新技术来实现成像 mRNA 分析，也许是最著名的“GFP 的 RNA 模拟物”，包括菠菜。荧光适体的亮度达到了现场使用的苛刻成像方法所需的新水平此外，我们将开发新的工程适体，以实现光控制。总体而言，该研究项目将增进我们对突触 mRNA 翻译的理解。神经元中的转录基因调控。

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Self-Assembly of Intracellular Multivalent RNA Complexes Using Dimeric Corn and Beetroot Aptamers.

DOI：
10.1021/jacs.1c13583
发表时间：
2022-03-30
期刊：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
影响因子：
15
作者：
Wu, Jiahui;Svensen, Nina;Song, Wenjiao;Kim, Hyaeyeong;Zhang, Sulei;Li, Xing;Jaffrey, Samie R.
通讯作者：
Jaffrey, Samie R.

Trans ligation of RNAs to generate hybrid circular RNAs using highly efficient autocatalytic transcripts.