Oxidation of cellular amino acid pools leads to cytotoxic mistranslation of the genetic code

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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 versus 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.

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Tammy Bullwinkle

Ohio State University, Columbus, United States

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The authors declare that no competing interests exist.
Noah M Reynolds

Ohio State University, Columbus, United States

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Medha Raina

Ohio State University, Columbus, United States

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Adil B Moghal

Ohio State University, Columbus, United States

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Eleftheria Matsa

Ohio State University, Columbus, United States

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Andrei Rajkovic

Ohio State University, Columbus, United States

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Huseyin Kayadibi

Adana Military Hospital, Adana, Turkey

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Farbod Fazlollahi

Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, United States

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Christopher Ryan

California Department of Toxic Substances Control, Los Angeles, United States

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Nathaniel Howitz

University of California, Los Angeles, Los Angeles, United States

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Kym F Faull

Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, United States

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The authors declare that no competing interests exist.
Beth Lazazzera

University of California, Los Angeles, Los Angeles, United States

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Michael Ibba

Ohio State University, Columbus, United States

For correspondence
ibba.1@att.net

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The authors declare that no competing interests exist.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.