A Quantitative Systems Approach Reveals Dynamic Control of tRNA Modifications during Cellular Stress
Name
Chan-2010-A Quantitative Systems Approach Reveals Dynamic Control of tRNA Modifications during Cellular Stress.pdf
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Author(s)
Chan, Tsz Yan Clement
Dyavaiah, Madhu
DeMott, Michael S.
Taghizadeh, Koli
Dedon, Peter C.
Begley, Thomas J.
Date Issued
December 2010
Journal
PLoS Genetics
Publisher
Public Library of Science
Citation
Chan CTY, Dyavaiah M, DeMott MS, Taghizadeh K, Dedon PC, et al. (2010) A Quantitative Systems Approach Reveals Dynamic Control of tRNA Modifications during Cellular Stress. PLoS Genet 6(12): e1001247. doi:10.1371/journal.pgen.1001247
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Final published version
Abstract
Decades of study have revealed more than 100 ribonucleoside structures incorporated as post-transcriptional modifications mainly in tRNA and rRNA, yet the larger functional dynamics of this conserved system are unclear. To this end, we developed a highly precise mass spectrometric method to quantify tRNA modifications in Saccharomyces cerevisiae. Our approach revealed several novel biosynthetic pathways for RNA modifications and led to the discovery of signature changes in the spectrum of tRNA modifications in the damage response to mechanistically different toxicants. This is illustrated with the RNA modifications Cm, m[superscript 5]C, and m[superscript 2][subscript 2]G, which increase following hydrogen peroxide exposure but decrease or are unaffected by exposure to methylmethane sulfonate, arsenite, and hypochlorite. Cytotoxic hypersensitivity to hydrogen peroxide is conferred by loss of enzymes catalyzing the formation of Cm, m[superscript 5]C, and m[superscript 2][subscript 2]G, which demonstrates that tRNA modifications are critical features of the cellular stress response. The results of our study support a general model of dynamic control of tRNA modifications in cellular response pathways and add to the growing repertoire of mechanisms controlling translational responses in cells.
MIT Department
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1371/journal.pgen.1001247
