The MazF-regulon: a toolbox for the post-transcriptional stress response in Escherichia coli.

The MazF-regulon: a toolbox for the post-transcriptional stress response in Escherichia coli.
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DOI:
10.1093/nar/gkw115
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发表时间:
2016-08-19
影响因子:
14.9
通讯作者:
Moll I
Moll I
中科院分区:
生物学2区
文献类型:
--
作者:
Sauert M;Wolfinger MT;Vesper O;Müller C;Byrgazov K;Moll I

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灵活适应环境压力对于细菌至关重要。大肠杆菌中的高效转录后应激反应机制由毒素 MazF 控制。应激诱导激活后,核糖核酸内切酶 MazF 会处理一个独特的转录子集以及成熟核糖体中的 16S 核糖体 RNA。由于这些“应激核糖体”对 MazF 处理的 mRNA 具有特异性,因此翻译程序发生了变化。为了识别这种“MazF-调节子”,我们采用了 Poly-seq(多核糖体分级分离与 RNA-seq 分析相结合)并分析了 mazF 过表达后引入转录组和翻译组的变化。出乎意料的是,我们的结果表明相应的蛋白质产物参与所有细胞过程,并且对一般应激反应没有特别贡献。此外,我们的研究结果表明,翻译重编程是对严酷压力的快速反应,并强调选择性翻译作为基因表达的全球调控机制的重要性迄今为止被低估。考虑到已报道的毒素-抗毒素 (TA) 系统对持久性的影响,我们的结果表明,MazF 在严酷应激期间充当主要效应器,可能会在细菌群体内引入翻译异质性,从而刺激持久性细胞的形成。
Flexible adaptation to environmental stress is vital for bacteria. An energy-efficient post-transcriptional stress response mechanism in Escherichia coli is governed by the toxin MazF. After stress-induced activation the endoribonuclease MazF processes a distinct subset of transcripts as well as the 16S ribosomal RNA in the context of mature ribosomes. As these ‘stress-ribosomes’ are specific for the MazF-processed mRNAs, the translational program is changed. To identify this ‘MazF-regulon’ we employed Poly-seq (polysome fractionation coupled with RNA-seq analysis) and analyzed alterations introduced into the transcriptome and translatome after mazF overexpression. Unexpectedly, our results reveal that the corresponding protein products are involved in all cellular processes and do not particularly contribute to the general stress response. Moreover, our findings suggest that translational reprogramming serves as a fast-track reaction to harsh stress and highlight the so far underestimated significance of selective translation as a global regulatory mechanism in gene expression. Considering the reported implication of toxin-antitoxin (TA) systems in persistence, our results indicate that MazF acts as a prime effector during harsh stress that potentially introduces translational heterogeneity within a bacterial population thereby stimulating persister cell formation.
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