Translational Control: Discovery and Mechanisms

翻译控制：发现和机制

• 批准号: 10152613
• 负责人: Andrei Korostelev
• 金额: $ 56.38万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10152613
• 关键词: Antibiotic Resistance; Antibiotics; Bacterial Infections; Communicable Diseases; Gene Expression; Gene Expression Regulation; Genetic Diseases; Genetic Transcription; Messenger RNA; Molecular; Mutation; Nonsense Mutation; Organism; Pathogenesis; Pathogenicity; Proteins; Regulation; Ribosomes; Signal Transduction; Stress; Structure; Terminator Codon; Translation Initiation; Translations; Viral; Virus; Virus Diseases; bacterial genetics; biological adaptation to stress; emerging antibiotic resistance; fight against; improved; infectious disease treatment; novel therapeutics

Project Summary/Abstract Ribosomes are at the center of gene expression regulation. Not only do they synthesize proteins, but they regulate transcription and respond to stress signals. The translational control underlies the pathogenesis of infectious and genetic diseases. Translation is a key antibiotic target, but the emergence of antibiotic resistance poses a serious challenge in the fight against infectious diseases. To improve our understanding of the translational control of gene expression in molecular detail, we propose to elucidate the structural mechanisms of (1) translation initiation of viral mRNAs and virus-like cellular mRNAs; (2) bacterial stress responses which couple translation with transcription, conferring bacterial pathogenicity and antibiotic resistance and (3) translation elongation and termination. Understanding these mechanisms may enable discovery of novel drugs for the treatment of viral or bacterial infections or genetic diseases caused by nonsense mutations.

项目摘要/摘要 核糖体是基因表达调控的中心。它们不仅合成了 蛋白质，但它们调节转录并对压力信号做出反应。平移控制 是传染病和遗传性疾病发病机制的基础。翻译是关键的抗生素 靶标，但抗生素耐药性的出现对抗击 传染病。为了提高我们对基因翻译控制的理解 在分子细节上的表达，我们建议阐明(1)的结构机制。 病毒mRNAs和病毒样细胞mRNAs的翻译起始；(2)细菌应激反应 它将翻译和转录结合在一起，赋予细菌致病性和抗生素 阻力和(3)平移伸长和终止。了解这些机制 可能使发现治疗病毒或细菌感染或遗传病的新药成为可能 由无义突变引起的疾病。