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Chimeric tRNAs as tools to induce proteome damage and identify components of stress responses

Misfolded proteins are caused by genomic mutations, aberrant splicing events, translation errors or environmental factors. The accumulation of misfolded proteins is a phenomenon connected to several human disorders, and is managed by stress responses specific to the cellular compartments being affec...

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Autores principales: Geslain, Renaud, Cubells, Laia, Bori-Sanz, Teresa, Álvarez-Medina, Roberto, Rossell, David, Martí, Elisa, de Pouplana, Lluís Ribas
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836549/
https://www.ncbi.nlm.nih.gov/pubmed/20007146
http://dx.doi.org/10.1093/nar/gkp1083
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author Geslain, Renaud
Cubells, Laia
Bori-Sanz, Teresa
Álvarez-Medina, Roberto
Rossell, David
Martí, Elisa
de Pouplana, Lluís Ribas
author_facet Geslain, Renaud
Cubells, Laia
Bori-Sanz, Teresa
Álvarez-Medina, Roberto
Rossell, David
Martí, Elisa
de Pouplana, Lluís Ribas
author_sort Geslain, Renaud
collection PubMed
description Misfolded proteins are caused by genomic mutations, aberrant splicing events, translation errors or environmental factors. The accumulation of misfolded proteins is a phenomenon connected to several human disorders, and is managed by stress responses specific to the cellular compartments being affected. In wild-type cells these mechanisms of stress response can be experimentally induced by expressing recombinant misfolded proteins or by incubating cells with large concentrations of amino acid analogues. Here, we report a novel approach for the induction of stress responses to protein aggregation. Our method is based on engineered transfer RNAs that can be expressed in cells or tissues, where they actively integrate in the translation machinery causing general proteome substitutions. This strategy allows for the introduction of mutations of increasing severity randomly in the proteome, without exposing cells to unnatural compounds. Here, we show that this approach can be used for the differential activation of the stress response in the Endoplasmic Reticulum (ER). As an example of the applications of this method, we have applied it to the identification of human microRNAs activated or repressed during unfolded protein stress.
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spelling pubmed-28365492010-03-11 Chimeric tRNAs as tools to induce proteome damage and identify components of stress responses Geslain, Renaud Cubells, Laia Bori-Sanz, Teresa Álvarez-Medina, Roberto Rossell, David Martí, Elisa de Pouplana, Lluís Ribas Nucleic Acids Res Methods Online Misfolded proteins are caused by genomic mutations, aberrant splicing events, translation errors or environmental factors. The accumulation of misfolded proteins is a phenomenon connected to several human disorders, and is managed by stress responses specific to the cellular compartments being affected. In wild-type cells these mechanisms of stress response can be experimentally induced by expressing recombinant misfolded proteins or by incubating cells with large concentrations of amino acid analogues. Here, we report a novel approach for the induction of stress responses to protein aggregation. Our method is based on engineered transfer RNAs that can be expressed in cells or tissues, where they actively integrate in the translation machinery causing general proteome substitutions. This strategy allows for the introduction of mutations of increasing severity randomly in the proteome, without exposing cells to unnatural compounds. Here, we show that this approach can be used for the differential activation of the stress response in the Endoplasmic Reticulum (ER). As an example of the applications of this method, we have applied it to the identification of human microRNAs activated or repressed during unfolded protein stress. Oxford University Press 2010-03 2009-12-08 /pmc/articles/PMC2836549/ /pubmed/20007146 http://dx.doi.org/10.1093/nar/gkp1083 Text en © The Author(s) 2009. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Methods Online
Geslain, Renaud
Cubells, Laia
Bori-Sanz, Teresa
Álvarez-Medina, Roberto
Rossell, David
Martí, Elisa
de Pouplana, Lluís Ribas
Chimeric tRNAs as tools to induce proteome damage and identify components of stress responses
title Chimeric tRNAs as tools to induce proteome damage and identify components of stress responses
title_full Chimeric tRNAs as tools to induce proteome damage and identify components of stress responses
title_fullStr Chimeric tRNAs as tools to induce proteome damage and identify components of stress responses
title_full_unstemmed Chimeric tRNAs as tools to induce proteome damage and identify components of stress responses
title_short Chimeric tRNAs as tools to induce proteome damage and identify components of stress responses
title_sort chimeric trnas as tools to induce proteome damage and identify components of stress responses
topic Methods Online
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836549/
https://www.ncbi.nlm.nih.gov/pubmed/20007146
http://dx.doi.org/10.1093/nar/gkp1083
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