Global tRNA misacylation induced by anaerobiosis and antibiotic exposure broadly increases stress resistance in Escherichia coli.
High translational fidelity is commonly considered a requirement for optimal cellular health and protein function. However, recent findings have shown that inducible mistranslation specifically with methionine engendered at the tRNA charging level occurs in mammalian cells, yeast and archaea, yet it was unknown whether bacteria were capable of mounting a similar response. Here, we demonstrate that Escherichia coli misacylates non-methionyl-tRNAs with methionine in response to anaerobiosis and antibiotic exposure via the methionyl-tRNA synthetase (MetRS). Two MetRS succinyl-lysine modifications independently confer high tRNA charging fidelity to the otherwise promiscuous, unmodified enzyme. Strains incapable of tRNA mismethionylation are less adept at growth in the presence of antibiotics and stressors. The presence of tRNA mismethionylation and its potential role in mistranslation within the bacterial domain establishes this response as a pervasive biological mechanism and connects it to diverse cellular functions and modes of fitness.
Department of Biochemistry and Molecular Biology, University of Chicago, 929 E. 57th St., Chicago, IL 60637, USA.|Committee on Microbiology, University of Chicago, 929 E. 57th St., Chicago, IL 60637, USA.
Michael H
MH
Schwartz
Department of Geophysical Sciences, University of Chicago, 5734 S. Ellis Ave., Chicago, IL 60637, USA.
Jacob R
JR
Waldbauer
Department of Geophysical Sciences, University of Chicago, 5734 S. Ellis Ave., Chicago, IL 60637, USA.
Lichun
L
Zhang
Department of Biochemistry and Molecular Biology, University of Chicago, 929 E. 57th St., Chicago, IL 60637, USA taopan@uchicago.edu.|Committee on Microbiology, University of Chicago, 929 E. 57th St., Chicago, IL 60637, USA.
Tao
T
Pan
D000215:Acylation; D000220:Adaptation, Biological / Q000235:genetics; D000595:Amino Acid Sequence; D000693:Anaerobiosis; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016000:Cluster Analysis; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D008718:Methionine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism; D008745:Methylation; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics
D000900:Anti-Bacterial Agents; D012343:RNA, Transfer; D008715:Methionine; D008718:Methionine-tRNA Ligase; D008239:Lysine
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