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

• 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
• 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

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.

项目概要 目前人们对骨骼肌干细胞（称为卫星细胞）的潜力非常感兴趣 可用于再生组织治疗。骨骼肌干细胞的分子认识 维持、命运决定和分化对于将研究转化为治疗至关重要 退行性肌肉疾病，几乎没有有效的治疗选择。该提案研究了如何 肌肉干细胞维持、更新和再生的程序是通过选择性、 由蛋白质 AUF1 指导加速 mRNA 降解。这是一个非常重要但基本上没有得到充分研究的问题 基因调控领域，在编程和控制成体组织干细胞命运和 组织再生。我们以之前的研究为基础，建议确定调节 AUF1 的因素 由于 AUF1 协调卫星的肌肉再生程序，因此在卫星细胞中表达 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 上演肌肉再生的不同发育事件，以及 AUF1 如何协调 通过与关键调节蛋白相互作用进行重编程，因为这控制着命运 确定卫星细胞从激活到肌肉再生的过程。