title: Oxidation of cellular amino acid pools leads to cytotoxic mistranslation of the genetic code.
abstract: Aminoacyl-tRNA synthetases use a variety of mechanisms to ensure fidelity of the genetic code and ultimately select the correct amino acids to be used in protein synthesis. The physiological necessity of these quality control mechanisms in different environments remains unclear, as the cost vs benefit of accurate protein synthesis is difficult to predict. We show that in Escherichia coli, a non-coded amino acid produced through oxidative damage is a significant threat to the accuracy of protein synthesis and must be cleared by phenylalanine-tRNA synthetase in order to prevent cellular toxicity caused by mis-synthesized proteins. These findings demonstrate how stress can lead to the accumulation of non-canonical amino acids that must be excluded from the proteome in order to maintain cellular viability.
authors.affiliation: Department of Microbiology, Ohio State University, Columbus, United States.
authors.forename: Tammy J
authors.initials: TJ
authors.lastname: Bullwinkle
authors.affiliation: Department of Microbiology, Ohio State University, Columbus, United States.
authors.forename: Noah M
authors.initials: NM
authors.lastname: Reynolds
authors.affiliation: Center for RNA Biology, Ohio State University, Columbus, United States.
authors.forename: Medha
authors.initials: M
authors.lastname: Raina
authors.affiliation: Center for RNA Biology, Ohio State University, Columbus, United States.
authors.forename: Adil
authors.initials: A
authors.lastname: Moghal
authors.affiliation: Department of Microbiology, Ohio State University, Columbus, United States.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Matsa
authors.affiliation: Center for RNA Biology, Ohio State University, Columbus, United States.
authors.forename: Andrei
authors.initials: A
authors.lastname: Rajkovic
authors.affiliation: Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States.
authors.forename: Huseyin
authors.initials: H
authors.lastname: Kayadibi
authors.affiliation: Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States.
authors.forename: Farbod
authors.initials: F
authors.lastname: Fazlollahi
authors.affiliation: Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Ryan
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Howitz
authors.affiliation: Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States.
authors.forename: Kym F
authors.initials: KF
authors.lastname: Faull
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Lazazzera
authors.affiliation: Department of Microbiology, Ohio State University, Columbus, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Ibba
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry*; D004926:Escherichia coli / Q000235:genetics; D005815:Genetic Code; D006868:Hydrolysis; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry*; D010652:Phenylalanine-tRNA Ligase / Q000235:genetics; D010957:Plasmids; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry; D020543:Proteome; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics
chemical_list: D000596:Amino Acids; D011506:Proteins; D020543:Proteome; D012346:RNA, Transfer, Amino Acyl; D000255:Adenosine Triphosphate; D000604:Amino Acyl-tRNA Synthetases; D010652:Phenylalanine-tRNA Ligase; D010100:Oxygen
keywords: E. coli; S. cerevisiae; biochemistry; infectious disease; microbiology; protein synthesis; stress; translation