Diverse molecular mechanisms of transcription regulation by the bacterial alarmone ppGpp.
Diverse molecular mechanisms of transcription regulation by the bacterial alarmone ppGpp.
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DOI：
10.1111/mmi.14860
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发表时间：
2022-03
影响因子：
3.6
通讯作者：
Schumacher, Maria A.
中科院分区：
文献类型：
--
作者：
Travis, Brady A.;Schumacher, Maria A.
细菌必须迅速发现并应对压力环境条件。鸟苷四磷酸（ppGpp）是一种普遍的应激信号，在大多数细菌中，它在全局水平上驱动转录的重编程。然而，最近的研究表明，ppGpp用于重新连接细菌转录组的分子机制出乎意料地多样化。在变形菌中，ppGpp通过直接结合RNA聚合酶（RNAP）上的两个位点来调节数百个基因的表达，其中一个与转录因子DksA结合。相反，ppGpp通过控制GTP水平间接调节厚壁菌门中的转录。在这种情况下，ppGpp抑制挽救和合成GTP的酶，这间接抑制rRNA和其他使用GTP启动的启动子的转录。最近，已经描述了涉及ppGpp直接结合转录因子的两种不同的转录调节机制。首先，在土拉热弗朗西斯菌中，ppGpp被证明可以调节结合RNAP并激活毒力基因的三重转录因子复合物的形成。第二，在厚壁菌门中，ppGpp变构调节转录阻遏物PurR，其控制嘌呤生物合成基因。这些研究中揭示的细菌ppGpp信号的多样性表明，ppGpp介导的转录调控中的其他范式可能有待发现。本文综述了ppGpp如何重新布线细菌转录组的最新分子机制研究结果。数据揭示了一个意想不到的机制，这是比较和对比，在这篇评论的多样性。
Bacteria must rapidly detect and respond to stressful environmental conditions. Guanosine tetraphosphate (ppGpp) is a universal stress signal that, in most bacteria, drives the reprograming of transcription at a global level. However, recent studies have revealed that the molecular mechanisms utilized by ppGpp to rewire bacterial transcriptomes are unexpectedly diverse. In Proteobacteria, ppGpp regulates the expression of hundreds of genes by directly binding to two sites on RNA polymerase (RNAP), one in combination with the transcription factor, DksA. Conversely, ppGpp indirectly regulates transcription in Firmicutes by controlling GTP levels. In this case, ppGpp inhibits enzymes that salvage and synthesize GTP, which indirectly represses transcription from rRNA and other promoters that use GTP for initiation. More recently, two different mechanisms of transcription regulation involving the direct binding of transcription factors by ppGpp have been described. First, in Francisella tularensis, ppGpp was shown to modulate the formation of a tripartite transcription factor complex that binds RNAP and activates virulence genes. Second, in Firmicutes, ppGpp allosterically regulates the transcription repressor, PurR, which controls purine biosynthesis genes. The diversity in bacterial ppGpp signaling revealed in these studies suggests the likelihood that additional paradigms in ppGpp‐mediated transcription regulation await discovery. This review covers recent molecular mechanistic findings on how ppGpp rewires bacterial transcriptomes. The data reveal an unexpected diversity of mechanisms, which are compared and contrasted in this review.
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