Highly Predictive Reprogramming of tRNA Modifications Is Linked to Selective Expression of Codon-Biased Genes
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Dedon_Highly predictive.pdf
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Author(s)
Begley, Thomas J.
Li, Fugen
Chan, Clement T. Y.
Deng, Wenjun
DeMott, Michael S
Babu, I. Ramesh
Dedon, Peter C
Date Issued
March 2015
Journal
Chemical Research in Toxicology
Publisher
American Chemical Society
Citation
Chan, Clement T. Y. et al. “Highly Predictive Reprogramming of tRNA Modifications Is Linked to Selective Expression of Codon-Biased Genes.” Chemical Research in Toxicology 28.5 (2015): 978–988. © 2015 American Chemical Society
Version
Final published version
Abstract
Cells respond to stress by controlling gene expression at several levels, with little known about the role of translation. Here, we demonstrate a coordinated translational stress response system involving stress-specific reprogramming of tRNA wobble modifications that leads to selective translation of codon-biased mRNAs representing different classes of critical response proteins. In budding yeast exposed to four oxidants and five alkylating agents, tRNA modification patterns accurately distinguished among chemically similar stressors, with 14 modified ribonucleosides forming the basis for a data-driven model that predicts toxicant chemistry with >80% sensitivity and specificity. tRNA modification subpatterns also distinguish S[subscript N]1 from S[subscript N]2 alkylating agents, with S[subscript N]2-induced increases in m[superscript 3]C in tRNA mechanistically linked to selective translation of threonine-rich membrane proteins from genes enriched with ACC and ACT degenerate codons for threonine. These results establish tRNA modifications as predictive biomarkers of exposure and illustrate a novel regulatory mechanism for translational control of cell stress response.
MIT Department
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/acs.chemrestox.5b00004
