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： 生物学的主要原则是通过遗传密码从核酸到蛋白质的准确信息流。人们普遍认为，在细胞中始终避免远离遗传密码的翻译。通过使用新的基因组方法，我们发现相反，哺乳动物细胞可以在先天免疫激活和化学触发的氧化应激后故意用氨基酸蛋氨酸对遗传密码进行编程。重新编程遗传代码是通过用蛋氨酸将非甲基二硫基因氨基化的氨基化来发生的，并且可诱导细胞中的活性氧（ROS）的调节产生。我们提出，通过调节的tRNA误导是通过调节的错误翻译是细胞应力反应的常见机制。我们将探索和检验关于用蛋氨酸对tRNA降低的生物学效应和功能的假设，并为所有氨基酸建立了全方位的tRNA误解及其参与哺乳动物细胞的翻译。此处获得的结果和概念理解应有助于建立一个新的错误翻译生物学领域。 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后故意用氨基酸蛋氨酸对遗传密码进行编程。在这里，我们旨在通过tRNA误导来建立错误翻译的生物学，作为哺乳动物细胞中应激反应的新机制。 科学审查官员准备了以下简历部分，以总结以下问题审查委员会讨论的结果。 委员会预算建议：根据要求建议预算。 科学评论官员指出： 由于NIH董事的先驱奖励申请与其他NIH赠款机制的审查不同，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以及以下有关RE的通知