Mis-translation as a new mechanism of stress response in biology

误译为生物学应激反应的新机制

• 批准号: 8337693
• 负责人: TAO PAN
• 金额: $ 78万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8337693
• 关键词: Amino Acids; Aminoacylation; Award; Biological; Biology; Budgets; Cells; Genetic Code; Genomics; Grant; Mammalian Cell; Methionine; Methods; Nucleic Acids; Outcome; Oxidative Stress; Production; Proteins; Reactive Oxygen Species; Recommendation; Review Committee; Testing; Time; Transfer RNA; Translations; United States National Institutes of Health; abstracting; biological adaptation to stress; immune activation; public health relevance

DESCRIPTION Abstract: A central tenet of biology is the accurate flow of information from nucleic acids to proteins through the genetic code. It is commonly believed that translation deviating from the genetic code is to be avoided at all times in cells. By using a new genomic method, we have discovered that in contrary, mammalian cells can deliberately reprogram the genetic code with the amino acid methionine upon innate immune activation and chemically triggered oxidative stress. Reprogramming the genetic code occurs through aminoacylation of non-methionyl-tRNAs with methionine, and is inducible upon regulated production of the reactive oxygen species (ROS) in the cell. We propose that mis-translation via regulated tRNA misacylation is a common mechanism for stress response for cells. We will explore and test hypotheses on biological effects and function on tRNA misacylation with methionine and establish a full spectrum of tRNA misacylation for all amino acids and their participations in translation in mammalian cells. The results and conceptual understanding obtained here shall help establish a new field of biology of mis-translation. Public Health Relevance: We have discovered that mammalian cells deliberately reprogram the genetic code with the amino acid methionine upon innate immune activation and oxidative stress. Here we aim to establish biology of mis-translation via tRNA misacylation as a new mechanism of stress response in mammalian cells. THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE ON THE FOLLOWING ISSUES. COMMITTEE BUDGET RECOMMENDATIONS: The budget was recommended as requested. SCIENTIFIC REVIEW OFFICERS NOTES: Since the NIH Director's Pioneer Award applications are reviewed differently from other NIH grant mechanisms, criterion scores and percentiles are not assigned. Please ignore the Administrative Budget Note on page one and the Notice below regarding re

描述 抽象的： 生物学的一个中心原则是信息通过遗传密码从核酸到蛋白质的准确流动。人们普遍认为，在细胞中应始终避免偏离遗传密码的翻译。通过使用新的基因组方法，我们发现，相反，哺乳动物细胞在先天免疫激活和化学触发的氧化应激下可以故意用氨基酸蛋氨酸重新编程遗传密码。遗传密码的重编程是通过用蛋氨酸对非蛋氨酰 tRNA 进行氨酰化来实现的，并且可以通过细胞中活性氧 (ROS) 的调节产生来诱导。我们认为，通过调节 tRNA 错酰化导致的错误翻译是细胞应激反应的常见机制。我们将探索和测试关于蛋氨酸 tRNA 错酰化的生物学效应和功能的假设，并建立所有氨基酸及其参与哺乳动物细胞翻译的全谱 tRNA 错酰化。这里获得的结果和概念理解将有助于建立误译生物学的新领域。 公共卫生相关性： 我们发现哺乳动物细胞在先天免疫激活和氧化应激时故意用氨基酸蛋氨酸重新编程遗传密码。在这里，我们的目标是通过 tRNA 错酰化建立错误翻译生物学，作为哺乳动物细胞应激反应的新机制。 以下简历部分由科学审查官员准备，以总结审查委员会关于以下问题的讨论结果。 委员会预算建议：预算是根据要求建议的。 科学审查官员注释： 由于 NIH 院长先锋奖申请的审查方式与其他 NIH 拨款机制不同，因此未分配标准分数和百分位数。 请忽略第一页的行政预算说明和下面有关重新调整的通知