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 摘要： 生物学的一个中心原则是通过遗传密码从核酸到蛋白质的准确信息流。通常认为，在细胞中应始终避免偏离遗传密码的翻译。通过使用一种新的基因组方法，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时故意用氨基酸甲硫氨酸重新编程遗传密码。基因密码的重编程通过非甲硫氨酰-tRNA与甲硫氨酸的氨酰化发生，并且在细胞中活性氧（ROS）的调节产生时是可诱导的。我们认为，通过调节tRNA的错酰化的错误翻译是细胞应激反应的一种常见机制。我们将探索和测试假设的生物学效应和功能的tRNA错酰化与甲硫氨酸，并建立一个完整的光谱的tRNA错酰化的所有氨基酸和它们的参与翻译在哺乳动物细胞。本文的研究结果和概念的理解将有助于建立一个新的误译生物学领域。 公共卫生相关性： 我们已经发现，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甲硫氨酸重编程遗传密码。在这里，我们的目标是建立生物学的错误翻译通过tRNA的错酰化作为一种新的机制，在哺乳动物细胞的应激反应。 以下简历部分由科学审查干事编写，概述了审查委员会就以下问题进行讨论的结果。 委员会预算建议：预算是按要求提出的。 科学审查官员注意到： 由于美国国立卫生研究院院长先锋奖的申请审查不同于其他美国国立卫生研究院拨款机制，标准分数和评分不分配。 请忽略第一页上的行政预算说明和下面关于重新分配的通知。