Small RNA Regulation in Bacteria

项目总结 细菌必须感知并对快速变化且往往充满压力的环境做出反应。他们制定法律的能力 改变细胞结构和功能的基因表达的快速变化是它们生存的关键。在过去的二十年里 多年来，已经非常清楚地表明，细菌中基因表达的转录后调控是 普遍存在，代表着一种重要的应激反应策略。碱基对的小RNA(sRNA 现在已知，mRNAs和调节转录延伸、翻译和mRNAs的稳定性是常见的 细菌转录后调节的介体。小RNA(SRNA)数量从几十到数百英寸 细菌基因组和执行不同的调控机制，但他们的活动和分子细节 它们在细菌生理和毒力中的具体作用仍然知之甚少。我的研究小组一直在 在过去的15年里一直致力于解决这些问题的研究。我们的总体方法是将 用基因组学方法结合经典遗传学和生物化学从分子到生物化学研究sRNA 大肠杆菌和沙门氏菌模型系统的生理水平。我们的工作确定了目标规则 揭示了一些新的sRNA介导的分子调控机制。我们有 发现了促进多靶点sRNA调控的分层调控的因素。我们也发现了压力 SRNA突变体的反应和代谢表型，将调节的分子机制联系到 生理结果。在下一个资助期，我们将建立一个强大和富有成效的基础， 继续研究大肠杆菌中sRNA依赖调控的新机制的先前工作和 沙门氏菌。我们将扩大我们的工作，调查这些监管机制的普遍性，并确定 新的例子。一个强大的合作者团队使用一套不同的技术将允许我们审问srna 在全球范围内和单个RNA分子水平上与靶mRNAs的相互作用。这将使我们能够 为sRNA的体内调控建立定量模型，并阐明广泛的sRNA调控 此外，我们还利用网络来制作比以往任何时候都更精确的SRNA相互作用图。我们设想继续 利用对sRNA的研究将分子生物学与细胞生理学联系起来，揭示对 微生物生物学。

PROJECT SUMMARY Bacteria must sense and respond to rapidly changing and often stressful environments. Their ability to enact rapid changes in gene expression that alter cell structure and function is key to their survival. In the last twenty years, it has become abundantly clear that post-transcriptional regulation of gene expression in bacteria is pervasive and represents an important stress response strategy. Small RNAs (sRNAs) that base pair with mRNAs and regulate transcription elongation, translation, and mRNA stability are now known to be common mediators of bacterial post-transcriptional regulation. Small RNAs (sRNAs) number from tens to hundreds in bacterial genomes and carry out diverse regulatory mechanisms, yet the molecular details of their activities and their specific roles in bacterial physiology and virulence remain poorly understood. My research group has been engaged in research to address these questions for the last 15 years. Our overall approach is to combine genomic approaches with classical genetics and biochemistry to study sRNAs from the molecular to the physiological level in Escherichia coli and Salmonella model systems. Our work has defined the target regulons of several sRNAs, revealing a number of new molecular mechanisms of sRNA-mediated regulation. We have uncovered factors that promote hierarchical regulation of multi-target sRNA regulons. We have also found stress response and metabolic phenotypes for sRNA mutants, linking the molecular mechanisms of regulation to physiological outcomes. In the next funding period, we will build on a strong and productive foundation of previous work to continue investigating novel mechanisms of sRNA-dependent regulation in E. coli and Salmonella. We will extend our work to investigate the prevalence of these regulatory mechanisms and identify new examples. A strong team of collaborators using a diverse set of techniques will allow us to interrogate sRNA interactions with target mRNAs on a global scale and at the level of single RNA molecules. This will allow us to generate quantitative models for in vivo regulation by sRNAs and elucidate an extensive sRNA regulatory network to produce an sRNA interaction map of greater precision than ever before. We envision continuing to use studies of sRNAs to connect molecular biology to cell physiology to reveal fundamental new insight into the biology of microbes.