Department of Chemistry, Lomonosov Moscow State University, Moscow 119992, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow 117997, Russia.
Nucleic Acids Res. 2020 Nov 4;48(19):10802-10819. doi: 10.1093/nar/gkaa798.
In bacteria, rapid adaptation to changing environmental conditions depends on the interplay between housekeeping and alternative σ factors, responsible for transcription of specific regulons by RNA polymerase (RNAP). In comparison with alternative σ factors, primary σs contain poorly conserved region 1.1, whose functions in transcription are only partially understood. We found that a single mutation in region 1.1 in Escherichia coli σ70 rewires transcription regulation during cell growth resulting in profound phenotypic changes. Despite its destabilizing effect on promoter complexes, this mutation increases the activity of rRNA promoters and also decreases RNAP sensitivity to the major regulator of stringent response DksA. Using total RNA sequencing combined with single-cell analysis of gene expression we showed that changes in region 1.1 disrupt the balance between the "greed" and "fear" strategies thus making the cells more susceptible to environmental threats and antibiotics. Our results reveal an unexpected role of σ region 1.1 in growth-dependent transcription regulation and suggest that changes in this region may facilitate rapid switching of RNAP properties in evolving bacterial populations.
在细菌中,快速适应不断变化的环境条件取决于管家基因和替代 σ 因子之间的相互作用,后者负责 RNA 聚合酶(RNAP)对特定调控子的转录。与替代 σ 因子相比,主要 σ 因子包含保守性较差的区域 1.1,其在转录中的功能仅部分被理解。我们发现,大肠杆菌 σ70 中的区域 1.1 中的单个突变在细胞生长过程中重新构建了转录调控,导致表型发生深刻变化。尽管该突变对启动子复合物具有不稳定作用,但它增加了 rRNA 启动子的活性,并且还降低了 RNAP 对严格反应主要调节剂 DksA 的敏感性。我们使用总 RNA 测序并结合单细胞基因表达分析表明,区域 1.1 的变化破坏了“贪婪”和“恐惧”策略之间的平衡,从而使细胞更容易受到环境威胁和抗生素的影响。我们的结果揭示了 σ 区域 1.1 在依赖生长的转录调控中的意外作用,并表明该区域的变化可能促进了进化中细菌种群中 RNAP 特性的快速切换。