Sauert Martina, Wolfinger Michael T, Vesper Oliver, Müller Christian, Byrgazov Konstantin, Moll Isabella
Max F. Perutz Laboratories, Center for Molecular Biology, Department of Microbiology, Immunobiology and Genetics, University of Vienna, Vienna Biocenter (VBC), Dr. Bohr-Gasse 9/4, A-1030 Vienna, Austria.
Max F. Perutz Laboratories, Department of Biochemistry and Molecular Cell Biology, University of Vienna, Vienna Biocenter (VBC), Dr. Bohr-Gasse 9/5, A-1030 Vienna, Austria Max F. Perutz Laboratories, Center for Integrative Bioinformatics Vienna, University of Vienna, Medical University of Vienna, Vienna Biocenter (VBC), Dr. Bohr-Gasse 9, A-1030 Vienna, Austria Institute for Theoretical Chemistry, University of Vienna, Währingerstraße 17, A-1090 Vienna, Austria.
Nucleic Acids Res. 2016 Aug 19;44(14):6660-75. doi: 10.1093/nar/gkw115. Epub 2016 Feb 22.
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.
对细菌而言，灵活适应环境压力至关重要。大肠杆菌中一种节能的转录后应激反应机制由毒素MazF调控。应激诱导激活后，核糖核酸内切酶MazF会在成熟核糖体的背景下加工特定的转录本子集以及16S核糖体RNA。由于这些“应激核糖体”对MazF加工的mRNA具有特异性，翻译程序会发生改变。为了鉴定这个“MazF调控子”，我们采用了Poly-seq（多核糖体分级分离与RNA测序分析相结合），并分析了mazF过表达后转录组和翻译组中引入的变化。出乎意料的是，我们的结果表明相应的蛋白质产物参与了所有细胞过程，对一般应激反应没有特别贡献。此外，我们的发现表明翻译重编程是对恶劣应激的快速反应，并突出了选择性翻译作为基因表达中一种全局调控机制迄今被低估的重要性。考虑到毒素-抗毒素（TA）系统在持续性方面的报道作用，我们的结果表明MazF在恶劣应激期间作为主要效应因子发挥作用，可能在细菌群体中引入翻译异质性，从而刺激持久细胞的形成。
