Accelerated and programmed mRNA decay by AU-rich binding protein AUF1 in the regulation of muscle regeneration

富含 AU 的结合蛋白 AUF1 在肌肉再生调节中加速和程序化 mRNA 降解

基本信息

批准号：
10061554
负责人：
Robert Schneider
金额：
$ 45.14万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-12-11 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10061554
关键词：
AUF1A protein Adult Aging Area Binding Proteins Cell Differentiation process Cell Maintenance Cell physiology Development Disease Event Gene Expression Regulation Genes Genetic Transcription Maintenance Mass Spectrum Analysis Mediating Messenger RNA Molecular Mus Muscle Muscle satellite cell Myoblasts Myopathy Natural regeneration Play Proteins Proteomics Regulation Research Role Skeletal Muscle Testing Therapeutic Tissue Therapy Transcriptional Activation Transcriptional Regulation Translating activating transcription factor effective therapy exhaustion genetic regulatory protein interest mRNA Decay muscle regeneration myogenesis programs protein protein interaction regenerative tissue satellite cell stem cell division stem cell fate stem cells tissue regeneration tissue stem cells transcription factor wound

AUF1A protein Adult Aging Area Binding Proteins Cell Differentiation process Cell Maintenance Cell physiology Development Disease Event Gene Expression Regulation Genes Genetic Transcription Maintenance Mass Spectrum Analysis Mediating Messenger RNA Molecular Mus Muscle Muscle satellite cell Myoblasts Myopathy Natural regeneration Play Proteins Proteomics Regulation Research Role Skeletal Muscle Testing Therapeutic Tissue Therapy Transcriptional Activation Transcriptional Regulation Translating activating transcription factor effective therapy exhaustion genetic regulatory protein interest mRNA Decay muscle regeneration myogenesis programs protein protein interaction regenerative tissue satellite cell stem cell division stem cell fate stem cells tissue regeneration tissue stem cells transcription factor wound

展开

项目摘要

Project Summary There is currently significant interest in the potential for skeletal muscle stem cells, known as satellite cells, to be used in regenerative tissue therapy. The molecular understanding of skeletal muscle stem cell maintenance, fate determination and differentiation is crucial for translating research to the treatment of degenerative muscle diseases where there are few effective treatment options. This proposal investigates how the program of muscle stem cell maintenance, renewal and regeneration are orchestrated by selective, accelerated mRNA decay directed by the protein AUF1. This is a highly important but largely understudied area of gene regulation that plays a major role in programming and controlling adult tissue stem cell fate and tissue regeneration. We build on our previous studies and propose to identify the factors that regulate AUF1 expression in the satellite cell because AUF1 orchestrates the muscle regeneration program of the satellite cell, identify the satellite cell mRNAs selectively targeted for rapid degradation by AUF1 because this appears to stage the different developmental events of muscle regeneration, and how AUF1 orchestrates the progression of reprogramming by interacting with key regulatory proteins because this controls fate determination of satellite cells from activation to muscle regeneration.

项目摘要目前，目前对骨骼肌干细胞（称为卫星细胞）的潜力引起了重大兴趣用于再生组织治疗。骨骼肌干细胞的分子理解维持，命运确定和差异化对于将研究转化为处理至关重要退化性肌肉疾病很少有有效的治疗选择。该建议调查了如何肌肉干细胞维护，更新和再生的程序由选择性策划，蛋白AUF1指导的加速mRNA衰变。这是一个非常重要的，但在很大程度上被研究了基因调节区域在编程和控制成人组织干细胞命运和组织再生。我们以先前的研究为基础，并建议确定调节AUF1的因素在卫星细胞中的表达是因为AUF1精心策划了卫星的肌肉再生程序细胞，识别选择性靶向AUF1快速降解的卫星细胞mRNA，因为这似乎是为肌肉再生的不同发育事件以及AUF1如何策划通过与关键调节蛋白相互作用，重新编程的进展，因为这控制了命运确定卫星细胞从激活到肌肉再生。