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

当它们进入新的环境，例如人体或供水系统时，细菌会通过改变它们的基因表达模式来迅速适应。这个项目将分析一类知之甚少的调节器，它们可能对许多细菌物种的基因表达变化很重要，如果不是大多数的话。本研究将分为培养本科生和硕士生的不同项目。研究成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相关的具体推广计划传达给社区。该中心致力于为经济困难和为少数族裔服务的科罗拉多州公立学区促进科学教育和实践经验。基因转录是一个高度受控的过程，确保只表达特定情况下所需的基因。转录被认为只发生在产生蛋白质编码的mRNAs、核糖体RNAs和转移RNAs的基因上。然而，在过去的十年中，非编码调控RNA已经成为一类新的转录遗传元件。最近，观察到基因组的很大一部分被转录；这种全基因组转录被称为普遍转录。普遍转录最初被认为是非功能噪音；然而，现在有证据表明，普遍转录是有功能的。本项目的目的是阐明广泛存在的转录本对基因调控的功能和分子机制，这些转录本是研究得很好、遗传上容易控制的模式生物大肠杆菌。传统的功能丧失反向遗传分析在这些RNA上执行是具有挑战性的，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存在的记录的删除。这些缺失菌株将使我们能够探索普遍存在的RNA在基因调控中的作用，并剖析其调控的分子机制。了解普遍转录在大肠杆菌基因表达中的调控作用及其使用的机制也将有助于深入了解其他细菌以及真核生物的基因调控策略，因为普遍转录的性质遍及生命的所有领域。

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.