Oxidation of cellular amino acid pools leads to cytotoxic mistranslation of the genetic code
Tammy J Bullwinkle,
Noah M Reynolds,
Medha Raina,
Adil Moghal,
Eleftheria Matsa,
Andrei Rajkovic,
Huseyin Kayadibi,
Farbod Fazlollahi,
Christopher Ryan,
Nathaniel Howitz,
Kym F Faull,
Beth A Lazazzera,
Michael Ibba
Affiliations
Tammy J Bullwinkle
Department of Microbiology, Ohio State University, Columbus, United States
Noah M Reynolds
Department of Microbiology, Ohio State University, Columbus, United States; Center for RNA Biology, Ohio State University, Columbus, United States
Medha Raina
Center for RNA Biology, Ohio State University, Columbus, United States; Ohio State Biochemistry Program, Ohio State University, Columbus, United States
Adil Moghal
Center for RNA Biology, Ohio State University, Columbus, United States; Ohio State Biochemistry Program, Ohio State University, Columbus, United States
Eleftheria Matsa
Department of Microbiology, Ohio State University, Columbus, United States
Andrei Rajkovic
Center for RNA Biology, Ohio State University, Columbus, United States; Molecular, Cellular and Developmental Biology Program, Ohio State University, Columbus, United States
Huseyin Kayadibi
Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States
Farbod Fazlollahi
Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States
Christopher Ryan
Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States
Nathaniel Howitz
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Kym F Faull
Pasarow Mass Spectrometry Laboratory, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, United States
Beth A Lazazzera
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Michael Ibba
Department of Microbiology, Ohio State University, Columbus, United States; Center for RNA Biology, Ohio State University, Columbus, United States; Ohio State Biochemistry Program, Ohio State University, Columbus, United States; Molecular, Cellular and Developmental Biology Program, Ohio State University, Columbus, United States
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.
