Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
J Bacteriol. 2017 Dec 20;200(2). doi: 10.1128/JB.00463-17. Print 2018 Jan 15.
σ is an alternative sigma factor, encoded by the gene, that redirects cellular transcription to a large family of genes in response to stressful environmental signals. This so-called σ general stress response is necessary for survival in many bacterial species and is controlled by a complex, multifactorial pathway that regulates σ levels transcriptionally, translationally, and posttranslationally in It was shown previously that the transcription factor DksA and its cofactor, ppGpp, are among the many factors governing σ synthesis, thus playing an important role in activation of the σ stress response. However, the mechanisms responsible for the effects of DksA and ppGpp have not been elucidated fully. We describe here how DksA and ppGpp directly activate the promoters for the anti-adaptor protein IraP and the small regulatory RNA DsrA, thereby indirectly influencing σ levels. In addition, based on effects of DksA, a previously identified DksA variant with increased affinity for RNA polymerase (RNAP), we show that DksA can increase σ activity by another indirect mechanism. We propose that by reducing rRNA transcription, DksA and ppGpp increase the availability of core RNAP for binding to σ and also increase transcription from other promoters, including P and P By improving the translation and stabilization of σ, as well as the ability of other promoters to compete for RNAP, DksA and ppGpp contribute to the switch in the transcription program needed for stress adaptation. Bacteria spend relatively little time in log phase outside the optimized environment found in a laboratory. They have evolved to make the most of alternating feast and famine conditions by seamlessly transitioning between rapid growth and stationary phase, a lower metabolic mode that is crucial for long-term survival. One of the key regulators of the switch in gene expression that characterizes stationary phase is the alternative sigma factor σ Understanding the factors governing σ activity is central to unraveling the complexities of growth, adaptation to stress, and pathogenesis. Here, we describe three mechanisms by which the RNA polymerase binding factor DksA and the second messenger ppGpp regulate σ levels.
σ 是一种替代 σ 因子，由 基因编码，可在受到应激环境信号时将细胞转录重新定向到一大类基因。这种所谓的 σ 一般应激反应对于许多细菌物种的生存是必要的，并且受到一个复杂的、多因素的途径控制，该途径在转录、翻译和翻译后水平上调节 σ 的水平。先前已经表明，转录因子 DksA 及其辅助因子 ppGpp 是调节 σ 合成的众多因素之一，因此在 σ 应激反应的激活中发挥重要作用。然而，DksA 和 ppGpp 的作用机制尚未完全阐明。我们在这里描述了 DksA 和 ppGpp 如何直接激活抗接头蛋白 IraP 和小调节 RNA DsrA 的启动子，从而间接影响 σ 水平。此外，基于 DksA 的影响，我们展示了一种先前鉴定的具有增加的 RNA 聚合酶 (RNAP) 亲和力的 DksA 变体如何通过另一种间接机制增加 σ 活性。我们提出，通过减少 rRNA 转录，DksA 和 ppGpp 增加了核心 RNAP 与 σ 结合的可用性，并增加了来自其他启动子的转录，包括 P 和 P。通过改善 σ 的翻译和稳定性，以及其他启动子竞争 RNAP 的能力，DksA 和 ppGpp 有助于适应应激所需的转录程序的转换。细菌在实验室中发现的优化环境之外相对很少时间处于对数期。它们通过在快速生长和静止期之间无缝过渡而进化，静止期是一种较低的代谢模式，对于长期生存至关重要，从而充分利用了交替的丰饶和饥荒条件。标志着静止期特征的基因表达转换的关键调节剂之一是替代 σ 因子 σ。理解调节 σ 活性的因素对于揭示生长、适应应激和发病机制的复杂性至关重要。在这里，我们描述了 RNA 聚合酶结合因子 DksA 和第二信使 ppGpp 调节 σ 水平的三种机制。
