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

• 批准号: 9924678
• 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
• 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
• 来源: https://reporter.nih.gov/project-details/9924678
• 关键词: Animals; Area; Biology; Brain; CGG repeat; Complementary DNA; Disease; Engineering; Epigenetic Process; Fragile X Syndrome; Genetic Translation; Goals; Hybrids; Image; Knowledge; Laboratories; Light; Messenger RNA; Modification; Neurologic; Neurons; Nucleotides; Pathway interactions; Pattern; Post-Transcriptional Regulation; Protein Biosynthesis; RNA; Regulation; Research; Research Support; Role; Spinach - dietary; Synapses; Synaptic plasticity; Technology; aptamer; base; epitranscriptomics; imaging approach; insight; mRNA Expression; neural circuit; new technology; novel; novel strategies; programs; synaptic function; transcriptome

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