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A System of RNA Modifications and Biased Codon Use Controls Cellular Stress Response at the Level of Translation

[Image: see text] Cells respond to environmental stressors and xenobiotic exposures using regulatory networks to control gene expression, and there is an emerging appreciation for the role of numerous postsynthetic chemical modifications of DNA, RNA, and proteins in controlling transcription and tra...

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Autores principales: Dedon, Peter C., Begley, Thomas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997223/
https://www.ncbi.nlm.nih.gov/pubmed/24422464
http://dx.doi.org/10.1021/tx400438d
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author Dedon, Peter C.
Begley, Thomas J.
author_facet Dedon, Peter C.
Begley, Thomas J.
author_sort Dedon, Peter C.
collection PubMed
description [Image: see text] Cells respond to environmental stressors and xenobiotic exposures using regulatory networks to control gene expression, and there is an emerging appreciation for the role of numerous postsynthetic chemical modifications of DNA, RNA, and proteins in controlling transcription and translation of the stress response. In this Perspective, we present a model for a new network that regulates the cellular response to xenobiotic exposures and other stresses in which stress-induced reprogramming of a system of dozens of post-transcriptional modifications on tRNA (tRNA) promotes selective translation of codon-biased mRNAs for critical response proteins. As a product of novel genomic and bioanalytical technologies, this model has strong parallels with the regulatory networks of DNA methylation in epigenetics and the variety of protein secondary modifications comprising signaling pathways and the histone code. When present at the tRNA wobble position, the modified ribonucleosides enhance the translation of mRNAs in which the cognate codons of the tRNAs are highly over-represented and that represent critical stress response proteins. A parallel system may also downregulate the translation of families of proteins. Notably, dysregulation of the tRNA methyltransferase enzymes in humans has also been implicated in cancer etiology, with demonstrated oncogenic and tumor-suppressive effects.
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spelling pubmed-39972232015-01-14 A System of RNA Modifications and Biased Codon Use Controls Cellular Stress Response at the Level of Translation Dedon, Peter C. Begley, Thomas J. Chem Res Toxicol [Image: see text] Cells respond to environmental stressors and xenobiotic exposures using regulatory networks to control gene expression, and there is an emerging appreciation for the role of numerous postsynthetic chemical modifications of DNA, RNA, and proteins in controlling transcription and translation of the stress response. In this Perspective, we present a model for a new network that regulates the cellular response to xenobiotic exposures and other stresses in which stress-induced reprogramming of a system of dozens of post-transcriptional modifications on tRNA (tRNA) promotes selective translation of codon-biased mRNAs for critical response proteins. As a product of novel genomic and bioanalytical technologies, this model has strong parallels with the regulatory networks of DNA methylation in epigenetics and the variety of protein secondary modifications comprising signaling pathways and the histone code. When present at the tRNA wobble position, the modified ribonucleosides enhance the translation of mRNAs in which the cognate codons of the tRNAs are highly over-represented and that represent critical stress response proteins. A parallel system may also downregulate the translation of families of proteins. Notably, dysregulation of the tRNA methyltransferase enzymes in humans has also been implicated in cancer etiology, with demonstrated oncogenic and tumor-suppressive effects. American Chemical Society 2014-01-14 2014-03-17 /pmc/articles/PMC3997223/ /pubmed/24422464 http://dx.doi.org/10.1021/tx400438d Text en Copyright © 2014 American Chemical Society
spellingShingle Dedon, Peter C.
Begley, Thomas J.
A System of RNA Modifications and Biased Codon Use Controls Cellular Stress Response at the Level of Translation
title A System of RNA Modifications and Biased Codon Use Controls Cellular Stress Response at the Level of Translation
title_full A System of RNA Modifications and Biased Codon Use Controls Cellular Stress Response at the Level of Translation
title_fullStr A System of RNA Modifications and Biased Codon Use Controls Cellular Stress Response at the Level of Translation
title_full_unstemmed A System of RNA Modifications and Biased Codon Use Controls Cellular Stress Response at the Level of Translation
title_short A System of RNA Modifications and Biased Codon Use Controls Cellular Stress Response at the Level of Translation
title_sort system of rna modifications and biased codon use controls cellular stress response at the level of translation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997223/
https://www.ncbi.nlm.nih.gov/pubmed/24422464
http://dx.doi.org/10.1021/tx400438d
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