title: A Stress-Induced Bias in the Reading of the Genetic Code in Escherichia coli.
abstract: Escherichia coli mazEF is an extensively studied stress-induced toxin-antitoxin (TA) system. The toxin MazF is an endoribonuclease that cleaves RNAs at ACA sites. Thereby, under stress, the induced MazF generates a stress-induced translation machinery (STM), composed of MazF-processed mRNAs and selective ribosomes that specifically translate the processed mRNAs. Here, we further characterized the STM system, finding that MazF cleaves only ACA sites located in the open reading frames of processed mRNAs, while out-of-frame ACAs are resistant. This in-frame ACA cleavage of MazF seems to depend on MazF binding to an extracellular-death-factor (EDF)-like element in ribosomal protein bS1 (bacterial S1), apparently causing MazF to be part of STM ribosomes. Furthermore, due to the in-frame MazF cleavage of ACAs under stress, a bias occurs in the reading of the genetic code causing the amino acid threonine to be encoded only by its synonym codon ACC, ACU, or ACG, instead of by ACA.
  
  
  
  The genetic code is a universal characteristic of all living organisms. It defines the set of rules by which nucleotide triplets specify which amino acid will be incorporated into a protein. Our results represent the first existing report on a stress-induced bias in the reading of the genetic code. We found that in E. coli, under stress, the amino acid threonine is encoded only by its synonym codon ACC, ACU, or ACG, instead of by ACA. This is because under stress, MazF generates a stress-induced translation machinery (STM) in which MazF cleaves in-frame ACA sites of the processed mRNAs.
authors.affiliation: Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Adi
authors.initials: A
authors.lastname: Oron-Gottesman
authors.affiliation: Department of Microbiology, Max F. Perutz Laboratories, Center for Molecular Biology, Immunobiology and Genetics, University of Vienna, Vienna, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Sauert
authors.affiliation: Department of Microbiology, Max F. Perutz Laboratories, Center for Molecular Biology, Immunobiology and Genetics, University of Vienna, Vienna, Austria.
authors.forename: Isabella
authors.initials: I
authors.lastname: Moll
authors.affiliation: Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel hanita@cc.huji.ac.il.
authors.forename: Hanna
authors.initials: H
authors.lastname: Engelberg-Kulka
mesh_terms: D018834:Chaperonin 60 / Q000235:genetics; D003062:Codon; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005815:Genetic Code; D016366:Open Reading Frames; D014176:Protein Biosynthesis / Q000235:genetics; D012329:RNA, Bacterial / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics; D012270:Ribosomes / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics*; D013379:Substrate Specificity; D013912:Threonine / Q000235:genetics
chemical_list: D018834:Chaperonin 60; D003062:Codon; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C422955:MazF protein, E coli; D012329:RNA, Bacterial; D012333:RNA, Messenger; D012269:Ribosomal Proteins; C544829:ribosomal protein S1, E coli; D013912:Threonine; D004722:Endoribonucleases