title: The MazF-regulon: a toolbox for the post-transcriptional stress response in Escherichia coli.
abstract: 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.
authors.affiliation: 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.
authors.forename: Martina
authors.initials: M
authors.lastname: Sauert
authors.affiliation: 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.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Wolfinger
authors.affiliation: 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.
authors.forename: Oliver
authors.initials: O
authors.lastname: Vesper
authors.affiliation: 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Müller
authors.affiliation: 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.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Byrgazov
authors.affiliation: 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 Isabella.moll@univie.ac.at.
authors.forename: Isabella
authors.initials: I
authors.lastname: Moll
mesh_terms: D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004722:Endoribonucleases / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics; D012313:RNA / Q000302:isolation & purification; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018085:Regulon / Q000235:genetics*; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA; D013312:Stress, Physiological / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C422955:MazF protein, E coli; D012333:RNA, Messenger; D012313:RNA; D004722:Endoribonucleases