Sangam: A Confluence of Knowledge Streams

tRNA modifications regulate translation during cellular stress

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dc.contributor Massachusetts Institute of Technology. Center for Environmental Health Sciences
dc.contributor Massachusetts Institute of Technology. Department of Biological Engineering
dc.contributor Gu, Chen
dc.contributor Dedon, Peter C.
dc.creator Gu, Chen
dc.creator Begley, Thomas J.
dc.creator Dedon, Peter C.
dc.date 2015-12-14T01:39:26Z
dc.date 2015-12-14T01:39:26Z
dc.date 2014-10
dc.date 2014-09
dc.date.accessioned 2023-03-01T18:10:56Z
dc.date.available 2023-03-01T18:10:56Z
dc.identifier 00145793
dc.identifier 1873-3468
dc.identifier http://hdl.handle.net/1721.1/100224
dc.identifier Gu, Chen, Thomas J. Begley, and Peter C. Dedon. “tRNA Modifications Regulate Translation During Cellular Stress.” FEBS Letters 588, no. 23 (November 2014): 4287–4296.
dc.identifier https://orcid.org/0000-0003-0011-3067
dc.identifier https://orcid.org/0000-0001-9920-2080
dc.identifier.uri http://localhost:8080/xmlui/handle/CUHPOERS/279059
dc.description The regulation of gene expression in response to stress is an essential cellular protection mechanism. Recent advances in tRNA modification analysis and genome-based codon bias analytics have facilitated studies that lead to a novel model for translational control, with translation elongation dynamically regulated during stress responses. Stress-induced increases in specific anticodon wobble bases are required for the optimal translation of stress response transcripts that are significantly biased in the use of degenerate codons keyed to these modified tRNA bases. These findings led us to introduce the notion of tRNA modification tunable transcripts (MoTTs – transcripts whose translation is regulated by tRNA modifications), which are identifiable using genome-wide codon counting algorithms. In support of this general model of translational control of stress response, studies making use of detailed measures of translation, tRNA methyltransferase mutants, and computational and mass spectrometry approaches reveal that stress reprograms tRNA modifications to translationally regulate MoTTs linked to arginine and leucine codons, which helps cells survive insults by damaging agents. These studies highlight how tRNA methyltransferase activities and MoTTs are key components of the cellular stress response.
dc.description National Science Foundation (U.S.) (CHE-1308839)
dc.description Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology Center. Infectious Disease Research Program)
dc.description David H. Koch Cancer Research Fund (Graduate Fellowship)
dc.description Howard Hughes Medical Institute (International Student Research Fellowship)
dc.format application/pdf
dc.language en_US
dc.publisher Elsevier
dc.relation http://dx.doi.org/10.1016/j.febslet.2014.09.038
dc.relation FEBS Letters
dc.rights Creative Commons Attribution
dc.rights http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.source PMC
dc.title tRNA modifications regulate translation during cellular stress
dc.type Article
dc.type http://purl.org/eprint/type/JournalArticle


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