Mechanism, Activation, and Control of rRNA Transcription

负责制造蛋白质的机制(如核糖体RNA、核糖体蛋白、翻译因子、 和tRNAs)对所有生物体的生长和发育都是至关重要的。对其合成的控制一直是一个 近60年来分子微生物学的核心问题。在以前的项目期间，这一点已经变得很清楚 我们的工作不仅对于理解核糖体的合成，而且对于理解核糖体的 转录启动的一般机制。在过去的几年里，显而易见的是 调节rrna启动子的系统也直接调节多种其他启动子，许多 其中一些是没有预料到的，因为它们与蛋白质合成设备的联系并不明显。 然而，我们现在知道，调节rrna启动子的分子在整个细菌中都被利用 在英国，它们在致病性和传染性疾病中发挥关键作用，并对基因组做出贡献 维护和转录一样重要。在下一个项目期间，我们将(I)继续研究 DNA-RNAP相互作用有助于启动子中从封闭复合体向开放复合体的转变 机制，(Ii)探索特定启动子区域在定义转录起始点中的作用，(Iii) 继续我们对ppGpp和Dks A转录调控的研究，通过定义它们的结合位点 RNA聚合酶及其作用机制的确定，(Iv)通过这些扩展我们对控制的分析 分子到额外的启动子，以便了解什么是积极的区别于消极的 调节靶点，(V)继续研究RNA聚合酶组装因子CRI的作用机制， 以及(Vi)继续研究我们最近的发现，即大肠杆菌使一种类似于真核生物的结构 核仁。我们将扩大这些研究的范围，以探索其他潜在的远程相互作用 细菌染色体的一部分。

The machinery responsible for making proteins (e.g. ribosomal RNA, ribosomal proteins, translation factors, and tRNAs) is central to growth and development of all organisms. The control of its synthesis has been a central issue in molecular microbiolgy for almost 60 years. It had become clear in previous project periods that our work was central not only for understanding ribosome synthesis but also for understanding the mechanism of transcription initiation in general. What has become apparent in the last few years is that the systems that regulate rRNA promoters also directly regulate a wide variety of other promoters as well, many of which were not anticipated because their connection to the protein synthetic apparatus was not apparent. However, we now know that the molecules that regulate rRNA promoters are utilized throughout the bacterial kingdom, they play crucial roles in virulence and infectious disease, and they contribute to genome maintenance as well as to transcription. In the next project period, we will (i) continue our studies on the DNA-RNAP interactions that contribute to the transition from a closed to an open complex in the promoter mechanism, (ii) explore the role of specific promoter regions in defining the transcription start site, (iii) continue our examination of the control of transcription by ppGpp and DksA by defining their binding sites on RNA polymerase and determining their mechanism of action, (iv) expand our analysis of control by these molecules to additional promoters in order to understand what differentiates positively from negatively regulated targets, (v) continue studying the mechanism of action ofthe RNA polymerase assembly factor CrI, and (vi) continue studies on our recent discovery that E. coli makes a structure analogous to the eukaryotic nucleolus. We will expand these studies to explore other potential long-range interactions between distant parts of the bacterial chromosome.