The fitness of an individual bacterial cell is highly dependent upon the temporal tuning of gene expression levels when subjected to different environmental cues. Kinetic regulation of transcription initiation is a key step in modulating the levels of transcribed genes to promote bacterial survival. The initiation phase encompasses the binding of RNA polymerase (RNAP) to promoter DNA and a series of coupled protein-DNA conformational changes prior to entry into processive elongation. The time required to complete the initiation phase can vary by orders of magnitude and is ultimately dictated by the DNA sequence of the promoter. In this review, we aim to provide the required background to understand how promoter sequence motifs may affect initiation kinetics during promoter recognition and binding, subsequent conformational changes which lead to DNA opening around the transcription start site, and promoter escape. By calculating the steady-state flux of RNA production as a function of these effects, we illustrate that the presence/absence of a consensus promoter motif cannot be used in isolation to make conclusions regarding promoter strength. Instead, the entire series of linked, sequence-dependent structural transitions must be considered holistically. Finally, we describe how individual transcription factors take advantage of the broad distribution of sequence-dependent basal kinetics to either increase or decrease RNA flux.

中文翻译：

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启动子序列基序对转录起始动力学和调控的上下文相关影响

单个细菌细胞的适应度高度依赖于基因表达水平在不同环境线索下的时间调整。转录起始的动力学调节是调节转录基因水平以促进细菌存活的关键步骤。起始阶段包括 RNA 聚合酶 (RNAP) 与启动子 DNA 的结合以及一系列偶联的蛋白质-DNA 构象变化，然后再进入进行性延伸。完成起始阶段所需的时间可能会因数量级而异，最终取决于启动子的 DNA 序列。在这篇综述中，我们旨在提供所需的背景，以了解启动子序列基序如何影响启动子识别和结合过程中的起始动力学，随后的构象变化导致转录起始位点周围的 DNA 开放，启动子逃逸。通过计算作为这些效应函数的 RNA 生产的稳态通量，我们说明不能单独使用共有启动子基序的存在/不存在来得出关于启动子强度的结论。相反，必须从整体上考虑整个系列的链接的、依赖于序列的结构转变。最后，我们描述了个体转录因子如何利用序列依赖性基础动力学的广泛分布来增加或减少 RNA 通量。我们说明，不能单独使用共有启动子基序的存在/不存在来得出关于启动子强度的结论。相反，必须从整体上考虑整个系列的链接的、依赖于序列的结构转变。最后，我们描述了个体转录因子如何利用序列依赖性基础动力学的广泛分布来增加或减少 RNA 通量。我们说明，不能单独使用共有启动子基序的存在/不存在来得出关于启动子强度的结论。相反，必须从整体上考虑整个系列的链接的、依赖于序列的结构转变。最后，我们描述了个体转录因子如何利用序列依赖性基础动力学的广泛分布来增加或减少 RNA 通量。