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Systematic approaches to deciphering regulation and function of RNA editing in brain

破译大脑中 RNA 编辑调控和功能的系统方法

基本信息

批准号：
10748600
负责人：
Xinshu Grace Xiao
金额：
$ 8.59万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-01 至 2025-10-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10748600
关键词：
3&apos Untranslated Regions ASD patient Address Adenosine Affect Alzheimer&apos s Disease Amino Acid Sequence Amyotrophic Lateral Sclerosis Animals Area Autopsy Bioinformatics Biological Assay Brain Cells Code Cognition Collection Complement Data Data Set Development Disease Double-Stranded RNA Embryo Enzymes Evolution Future Gene Expression Regulation Genes Genetic Transcription Genomics Health Human Human Biology Individual Inosine Introns Life Malignant Neoplasms Mammals Membrane Mental Depression Messenger RNA Methodology Methods Modification Molecular Nervous System Neurobiology Neurodevelopmental Disorder Neurologic Dysfunctions Nucleotides Organism Pattern Phenotype Post-Transcriptional Regulation Primates Protein Family Proteins Publishing RNA RNA Editing RNA Processing RNA Sequences RNA analysis RNA-Binding Proteins Regulation Reporter Reporting Research Role Sampling Schizophrenia Series Signal Transduction Site Technology Testing Tissues Untranslated RNA Untranslated Regions Variant Work autism spectrum disorder biological systems cell type comparison control dsRNA adenosine deaminase experimental study genetic regulatory protein high throughput screening human disease insight neuropsychiatric disorder neurotransmission novel success transcriptome transcriptome sequencing

项目摘要

Project Summary Recent advances in sequencing technologies and bioinformatic methodologies have enabled great progress in better understanding RNA processing, regulation and modification. RNA editing is a prevalent type of RNA modification where the RNA sequences are altered through insertion, deletion or substitution of nucleotides. In mammals, the most common type of RNA editing is adenosine to inosine (A-to-I) editing. A-to-I editing is essential for normal life and development. A handful of A-to-I editing sites have been discovered with critical roles in neuronal signaling, by modulating membrane excitability, neurotransmission plasticity and signal transduction. In addition, aberrant RNA editing has been implicated in human neuropsychiatric diseases, such as Autism, Alzheimer’s disease, depression, schizophrenia, and amyotrophic lateral sclerosis. While numerous RNA editing sites have been identified via RNA-sequencing (RNA-seq) and related technologies, major challenges exist in understanding the function and regulation of RNA editing. The vast majority of known human RNA editing sites reside in non- coding regions, such as introns and untranslated regions, that may confer regulatory function to the related gene, especially at the level of post-transcriptional regulation. Therefore, there is a great demand for in-depth studies of the functional impacts of RNA editing on post- transcriptional regulation. The regulatory mechanisms of RNA editing are poorly characterized. Except the ADAR enzymes, few proteins and their mechanisms of action have been examined for RNA editing. A major challenge is the lack of efficient and systematic methods to pinpoint novel regulators. In this project, we propose to extend our recent success at developing bioinformatic and experimental frameworks to address the above challenges. We will capitalize on the large collection of RNA-seq data sets derived from postmortem brain samples. We will develop and apply novel methodologies to make full use of these data sets, complemented by further bioinformatic prediction and high-throughput experimental testing, to predict and validate the molecular function of RNA editing and related regulatory mechanisms. This work will allow a previously unattained level of understanding of the molecular basis of RNA editing and provide new insights to the involvement of RNA editing in human biology.

项目总结