Pervasive transcription in bacterial genomes

细菌基因组中的普遍转录

• 批准号: 7980955
• 负责人: Joseph Thomas Wade
• 金额: $ 243.05万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7980955
• 关键词: Animal Model; Bacteria; Bacterial Genes; Bacterial Genome; Bacterial Physiology; Code; Core Facility; DNA; Environment; Escherichia coli; Eukaryota; Functional RNA; Gene Expression; Gene Expression Regulation; Genes; Genetic Transcription; Genomics; Goals; MicroRNAs; Molecular and Cellular Biology; Pathogenesis; Proteins; Regulation; Research; Training; Transcript; Virulence; Work; bacterial genetics; interdisciplinary approach; novel; willingness

DESCRIPTION (Provided by the applicant) Abstract: We use Escherichia coli as a model organism to define the mechanisms of gene regulation in bacteria. Regulation of gene expression is a critical aspect of bacterial pathogenesis, and much of our understanding has come from studies of E. coli. The vast majority of work on gene expression has focused on protein regulators, but recent studies in eukaryotes have identified thousands of non-coding RNAs (ncRNAs), many of which have regulatory functions. We have recently identified over 1,000 novel transcripts in E. coli that initiate within protein-coding genes, on both DNA strands. We have strong evidence that many of these intragenic RNAs (iRNAs) have a regulatory function. Discovery of pervasive transcription of iRNAs fundamentally changes the established view of bacterial transcriptomes. The goal of this proposal is to determine whether pervasive iRNA transcription is an important, widespread, regulatory mechanism in bacteria, analogous to microRNAs in eukaryotes. To achieve this goal we will use a multidisciplinary approach to (i) comprehensively identify iRNAs, (ii) determine the mechanisms of regulation for key selected iRNA examples, (iii) determine the impact of gene regulation by iRNAs on virulence in a pathogenic strain of E. coli. We are ideally prepared to undertake this project due to my expertise and training in bacterial genetics and genomics, and my willingness to challenge long-standing paradigms in the field of bacterial gene regulation. The Wadsworth Center provides an outstanding environment for these studies because of its excellent research into bacteria and gene regulation, and a strong network of core facilities. The work proposed here will transform our understanding of bacterial gene expression and has major implications for the study of bacterial physiology and pathogenesis. Public Health Relevance: RNA has recently been recognized as a key regulator of gene expression. We have identified over 1,000 novel RNAs in the model bacterium, Escherichia coli. We will determine the impact of these RNAs on gene expression.

描述（申请人提供） 摘要：我们使用大肠杆菌作为模型生物来定义细菌基因调节的机制。基因表达的调节是细菌发病机理的关键方面，我们的大部分理解来自大肠杆菌的研究。关于基因表达的绝大多数工作都集中在蛋白质调节剂上，但是在真核生物的最新研究已经确定了数千个非编码RNA（NCRNA），其中许多具有调节功能。我们最近在两个DNA链上都确定了在蛋白质编码基因内启动的大肠杆菌中的1,000多种新型转录本。我们有强有力的证据表明，许多这些基因内RNA（IRNA）具有调节功能。 IRNA的普遍转录的发现从根本上改变了细菌转录组的既定观点。该提案的目的是确定普遍存在的IRNA转录是否是细菌中重要的，广泛的调节机制，类似于真核生物中的microRNA。为了实现这一目标，我们将使用多学科的方法来全面识别IRNA，（ii）确定关键选择的IRNA示例调节机制，（iii）确定IRNA对大肠杆菌致病菌株中毒力的基因调节对基因调节的影响。由于我在细菌遗传学和基因组学方面的专业知识和培训以及我愿意在细菌调节领域挑战长期存在的范式，因此我们准备进行该项目。 Wadsworth中心为这些研究提供了出色的环境，因为它对细菌和基因调节的出色研究以及强大的核心设施网络。这里提出的工作将改变我们对细菌基因表达的理解，并对细菌生理和发病机理的研究具有重要意义。 公共卫生相关性：RNA最近被公认为是基因表达的关键调节剂。我们已经在模型细菌Escherichia Coli中确定了1,000多种新型RNA。我们将确定这些RNA对基因表达的影响。

项目成果

Widespread suppression of intragenic transcription initiation by H-NS.

• DOI: 10.1101/gad.234336.113
• 发表时间: 2014-02-01
• 期刊: Genes & development
• 影响因子: 10.5
• 作者: Singh SS;Singh N;Bonocora RP;Fitzgerald DM;Wade JT;Grainger DC
• 通讯作者: Grainger DC

Identification of regulatory RNA in bacterial genomes by genome-scale mapping of transcription start sites.

通过转录起始位点的基因组规模作图来鉴定细菌基因组中的调节 RNA。

• DOI: 10.1007/978-1-62703-730-3_1
• 发表时间: 2014
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Singh,Navjot;Wade,JosephT
• 通讯作者: Wade,JosephT

Identification and characterization of small RNAs in Yersinia pestis.

• DOI: 10.4161/rna.23590
• 发表时间: 2013-03
• 期刊: RNA biology
• 影响因子: 4.1
• 作者: Beauregard A;Smith EA;Petrone BL;Singh N;Karch C;McDonough KA;Wade JT
• 通讯作者: Wade JT

Genome-Wide Transcriptional Response to Varying RpoS Levels in Escherichia coli K-12.

大肠杆菌 K-12 对不同 RpoS 水平的全基因组转录反应。

• DOI: 10.1128/jb.00755-16
• 发表时间: 2017
• 期刊: Journal of bacteriology
• 影响因子: 3.2
• 作者: Wong,GarrettT;Bonocora,RichardP;Schep,AliciaN;Beeler,SuzannahM;LeeFong,AnnaJ;Shull,LaurenM;Batachari,LakshmiE;Dillon,Moira;Evans,Ciaran;Becker,CarlaJ;Bush,EliotC;Hardin,Johanna;Wade,JosephT;Stoebel,DanielM
• 通讯作者: Stoebel,DanielM

Mapping the Regulatory Network for Salmonella enterica Serovar Typhimurium Invasion.

• DOI: 10.1128/mbio.01024-16
• 发表时间: 2016-09-06
• 期刊: mBio
• 影响因子: 6.4
• 作者: Smith C;Stringer AM;Mao C;Palumbo MJ;Wade JT
• 通讯作者: Wade JT