RUI: The Function and Molecular Mechanisms of Novel RNAs in E. Coli

RUI：大肠杆菌中新型 RNA 的功能和分子机制

• 批准号: 1516368
• 负责人: Meghan Lybecker
• 金额: $ 57.59万
• 依托单位: University of Colorado at Colorado Springs
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1516368&HistoricalAwards=false
• 关键词: RUI; Function; Molecular; Mechanisms; Novel

When they enter new environments, for example the human body or the water supply, bacteria quickly adapt by altering their gene expression patterns. This project will analyze a poorly understood class of regulators that may be important for such changes in gene expression in many if not most bacterial species. The research in this study will be divided into discrete projects for training undergraduate and Master's level students. The outcomes of the research will be conveyed to the community through specific outreach programs associated with the University of Colorado at Colorado Springs' Center for Science, Technology, Engineering and Mathematics Education. This Center is dedicated to promoting science education and hands-on experiences for economically disadvantaged and minority-serving Colorado public school districts.Gene transcription is a highly regulated process, ensuring that only the genes necessary in a particular situation are expressed. Transcription was thought to occur exclusively at genes producing protein-coding mRNAs, ribosomal RNAs, and transfer RNAs. However, in the past decade, non-coding regulatory RNAs have emerged as a new class of transcribed genetic elements. More recently, large portions of the genome have been observed to be transcribed; this genome-wide transcription was termed pervasive transcription. Pervasive transcription was initially considered to be non-functional noise; however, there is now evidence suggesting that pervasive transcripts are functional. The objective of this project is to elucidate the function and molecular mechanisms of gene regulation by pervasive transcripts in the well-studied and genetically tractable model organism Escherichia coli. Traditional loss-of-function reverse genetic assays are challenging to perform on these RNAs because they overlap (or are complementary to) annotated genes. Therefore innovative methods to construct deletions of pervasive transcripts will be employed. These deletion strains will allow us to probe the role of pervasive RNAs in gene regulation and to dissect the molecular mechanisms of their regulation. Understanding the regulatory roles of pervasive transcripts, and the mechanisms they employ, in gene expression in E. coli will also offer insight into the gene regulation strategies of other bacteria, as well as eukaryotes, due to the widespread nature of pervasive transcription across all domains of life.

当它们进入新的环境，例如人体或供水系统时，细菌通过改变它们的基因表达模式来迅速适应。 该项目将分析一类知之甚少的调节剂，这些调节剂可能对许多（如果不是大多数）细菌物种的基因表达变化很重要。 在这项研究中的研究将分为离散的项目，为培养本科生和硕士生水平的学生。 研究结果将通过与科罗拉多大学科罗拉多斯普林斯科学、技术、工程和数学教育中心有关的具体外展计划传达给社区。该中心致力于促进科学教育和实践经验，为经济上处于不利地位和少数民族服务的科罗拉多公立学校districts.基因转录是一个高度调控的过程，确保只有在特定情况下必要的基因表达。转录被认为只发生在产生蛋白质编码mRNA、核糖体RNA和转移RNA的基因上。然而，在过去的十年中，非编码调节RNA已经作为一类新的转录遗传元件出现。最近，已经观察到基因组的大部分被转录;这种全基因组转录被称为普适转录。普适转录最初被认为是非功能性噪音;然而，现在有证据表明普适转录是功能性的。本项目的目的是阐明基因调控的功能和分子机制的广泛的转录本在研究和遗传上易处理的模式生物大肠杆菌。传统的功能丧失反向遗传分析对这些RNA具有挑战性，因为它们与注释的基因重叠（或互补）。因此，将采用创新的方法来构建普遍转录物的缺失。这些缺失菌株将使我们能够探测普遍RNA在基因调控中的作用，并剖析其调控的分子机制。了解普适转录本在大肠杆菌基因表达中的调控作用及其机制。大肠杆菌也将提供深入了解其他细菌的基因调控策略，以及真核生物，由于普遍的转录在所有领域的生活。