A Quantitative Systems Approach Reveals Dynamic Control of tRNA Modifications during Cellular Stress
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...
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2011
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| Online Access: | http://hdl.handle.net/1721.1/64964 https://orcid.org/0000-0003-0011-3067 https://orcid.org/0000-0001-7940-3459 https://orcid.org/0000-0002-4607-5337 |
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| author | Chan, Tsz Yan Clement Dyavaiah, Madhu DeMott, Michael S. Taghizadeh, Koli Dedon, Peter C. Begley, Thomas J. |
| author2 | Massachusetts Institute of Technology. Center for Environmental Health Sciences |
| author_facet | Massachusetts Institute of Technology. Center for Environmental Health Sciences Chan, Tsz Yan Clement Dyavaiah, Madhu DeMott, Michael S. Taghizadeh, Koli Dedon, Peter C. Begley, Thomas J. |
| author_sort | Chan, Tsz Yan Clement |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:21:17Z |
| format | Article |
| id | mit-1721.1/64964 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:21:17Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/649642022-09-29T08:52:35Z A Quantitative Systems Approach Reveals Dynamic Control of tRNA Modifications during Cellular Stress Chan, Tsz Yan Clement Dyavaiah, Madhu DeMott, Michael S. Taghizadeh, Koli Dedon, Peter C. Begley, Thomas J. Massachusetts Institute of Technology. Center for Environmental Health Sciences Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemistry Dedon, Peter C. Chan, Tsz Yan Clement DeMott, Michael S. Taghizadeh, Koli Dedon, Peter C. 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. National Institute of Environmental Health Sciences (ES002109) National Institute of Environmental Health Sciences (ES017010) National Institute of Environmental Health Sciences (ES015037) National Cancer Institute (U.S.) (CA026731) National Center for Research Resources (U.S.) (RR023783) Singapore-MIT Alliance for Research and Technology 2011-07-28T15:06:26Z 2011-07-28T15:06:26Z 2010-12 2010-08 Article http://purl.org/eprint/type/JournalArticle 1553-7404 1553-7390 http://hdl.handle.net/1721.1/64964 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 https://orcid.org/0000-0003-0011-3067 https://orcid.org/0000-0001-7940-3459 https://orcid.org/0000-0002-4607-5337 en_US http://dx.doi.org/10.1371/journal.pgen.1001247 PLoS Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Chan, Tsz Yan Clement Dyavaiah, Madhu DeMott, Michael S. Taghizadeh, Koli Dedon, Peter C. Begley, Thomas J. A Quantitative Systems Approach Reveals Dynamic Control of tRNA Modifications during Cellular Stress |
| title | A Quantitative Systems Approach Reveals Dynamic Control of tRNA Modifications during Cellular Stress |
| title_full | A Quantitative Systems Approach Reveals Dynamic Control of tRNA Modifications during Cellular Stress |
| title_fullStr | A Quantitative Systems Approach Reveals Dynamic Control of tRNA Modifications during Cellular Stress |
| title_full_unstemmed | A Quantitative Systems Approach Reveals Dynamic Control of tRNA Modifications during Cellular Stress |
| title_short | A Quantitative Systems Approach Reveals Dynamic Control of tRNA Modifications during Cellular Stress |
| title_sort | quantitative systems approach reveals dynamic control of trna modifications during cellular stress |
| url | http://hdl.handle.net/1721.1/64964 https://orcid.org/0000-0003-0011-3067 https://orcid.org/0000-0001-7940-3459 https://orcid.org/0000-0002-4607-5337 |
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