Structural bases of the functions of RNA-protein machines - Project 2

RNA-蛋白质机器功能的结构基础 - 项目 2

• 批准号: 7782561
• 负责人: RONALD R BREAKER
• 金额: $ 27.33万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7782561
• 关键词: 5' Untranslated Regions; Adopted; Affinity; Amino Acids; Antibiotics; Bacteria; Bacterial Genes; Binding; Biochemical; Biochemical Genetics; Bioinformatics; Carrier Proteins; Cells; Cellular Assay; Characteristics; Chemicals; Coenzymes; Complex; Cues; Data; Development; Dialysis procedure; Dissection; Elements; Employee Strikes; Equilibrium; Eukaryota; Event; Exhibits; Figs - dietary; Future; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Carriers; Genetic Techniques; Genetic Transcription; Investigation; Laboratories; Lead; Life; Ligand Binding; Ligands; Messenger RNA; Metabolic; Metabolic Pathway; Metabolism; Methods; Molecular; Monitor; Nucleotides; Organism; Pattern; Phylogenetic Analysis; Physiological; Property; Proteins; RNA; RNA Sequences; Recording of previous events; Research; Resolution; Resources; Ribosomes; Role; Route; Second Messenger Systems; Sequence Analysis; Series; Signal Transduction; Small RNA; Specificity; Stimulus; Structural Biologist; Structure; System; Tetrahydrofolates; Therapeutic Uses; Translation Process; Translations; Work; antimicrobial drug; aptamer; base; comparative; drug development; empowered; insight; member; molecular recognition; novel; programs; research study; second messenger; stoichiometry; structural biology; sugar; three dimensional structure

essenger RNAs are typically thought of as passive carriers of genetic information that are acted upon by protein- or small RNA-regulatory factors and by ribosomes during the process of translation. Recently, we have found that the 5'-untranslated regions (UTRs) of numerous bacterial mRNAs serve a more proactive role in metabolic monitoring and genetic control. RNA genetic switches called riboswitches selectively bind metabolites without the need for proteins, and subsequently modulate gene expression by several distinct mechanisms. Riboswitches exhibit striking complexity in structure and action, and our findings indicate that cells from all three domains of life use these metabolite-sensing RNAs to control fundamental metabolic pathways. Furthermore, we have evidence that riboswitches or their components sometimes occur in tandem and that these arrangements lead to even greater gene control sophistication. We propose to continue our efforts to establish the basic features of new-found classes of riboswitches, with particular emphasis on the characterization of two novel classes that bind cyclic di-GMP and tetrahydrofolate. These analyses of the structural and functional characteristics of novel riboswitch systems are intended to establish the basic principles of riboswitch molecular recognition and function. Our findings will increase our understanding of bacterial gene control mechanisms, facilitate atomic-resolution structural analyses of riboswitch RNAs, and provide possible new targets for antimicrobial drug development.

Esenger RNA通常被认为是遗传信息的被动载体，由 蛋白质或小RNA调节因子和核糖体在翻译过程中起重要作用。最近，我们 已经发现大量细菌mRNAs的5‘-非翻译区(UTRs)服务于更主动的 在新陈代谢监测和遗传控制中的作用。被称为核糖开关的RNA遗传开关选择性地结合 代谢产物不需要蛋白质，随后通过几种不同的方式调节基因表达 机制。核糖开关在结构和作用上表现出惊人的复杂性，我们的发现表明 来自所有三个生命领域的细胞都使用这些代谢物感测RNA来控制基本代谢 小路。此外，我们有证据表明，核糖开关或其成分有时会出现在 这些安排导致了更高的基因控制复杂性。我们建议 继续努力确定新发现的核糖开关类型的基本特征，特别是 重点研究了两类结合环状双GMP和四氢叶酸的新型化合物的表征。这些 对新型核糖开关系统的结构和功能特征的分析旨在建立 核糖开关分子识别和功能的基本原理。我们的发现将增加我们的 了解细菌基因控制机制，促进原子分辨结构分析 核糖开关RNA，并为抗菌药物开发提供可能的新靶点。