hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma

RNA G-quadruplexes (RG4s) are four-stranded structures known to control mRNA translation of cancer relevant genes. RG4 formation is pervasive in vitro but not in cellulo, indicating the existence of poorly characterized molecular machinery that remodels RG4s and maintains them unfolded. Here, we per...

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Autores principales: Herviou, Pauline, Le Bras, Morgane, Dumas, Leïla, Hieblot, Corinne, Gilhodes, Julia, Cioci, Gianluca, Hugnot, Jean-Philippe, Ameadan, Alfred, Guillonneau, François, Dassi, Erik, Cammas, Anne, Millevoi, Stefania
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253433/
https://www.ncbi.nlm.nih.gov/pubmed/32461552
http://dx.doi.org/10.1038/s41467-020-16168-x
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author Herviou, Pauline
Le Bras, Morgane
Dumas, Leïla
Hieblot, Corinne
Gilhodes, Julia
Cioci, Gianluca
Hugnot, Jean-Philippe
Ameadan, Alfred
Guillonneau, François
Dassi, Erik
Cammas, Anne
Millevoi, Stefania
author_facet Herviou, Pauline
Le Bras, Morgane
Dumas, Leïla
Hieblot, Corinne
Gilhodes, Julia
Cioci, Gianluca
Hugnot, Jean-Philippe
Ameadan, Alfred
Guillonneau, François
Dassi, Erik
Cammas, Anne
Millevoi, Stefania
author_sort Herviou, Pauline
collection PubMed
description RNA G-quadruplexes (RG4s) are four-stranded structures known to control mRNA translation of cancer relevant genes. RG4 formation is pervasive in vitro but not in cellulo, indicating the existence of poorly characterized molecular machinery that remodels RG4s and maintains them unfolded. Here, we performed a quantitative proteomic screen to identify cytosolic proteins that interact with a canonical RG4 in its folded and unfolded conformation. Our results identified hnRNP H/F as important components of the cytoplasmic machinery modulating the structural integrity of RG4s, revealed their function in RG4-mediated translation and uncovered the underlying molecular mechanism impacting the cellular stress response linked to the outcome of glioblastoma.
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spelling pubmed-72534332020-06-05 hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma Herviou, Pauline Le Bras, Morgane Dumas, Leïla Hieblot, Corinne Gilhodes, Julia Cioci, Gianluca Hugnot, Jean-Philippe Ameadan, Alfred Guillonneau, François Dassi, Erik Cammas, Anne Millevoi, Stefania Nat Commun Article RNA G-quadruplexes (RG4s) are four-stranded structures known to control mRNA translation of cancer relevant genes. RG4 formation is pervasive in vitro but not in cellulo, indicating the existence of poorly characterized molecular machinery that remodels RG4s and maintains them unfolded. Here, we performed a quantitative proteomic screen to identify cytosolic proteins that interact with a canonical RG4 in its folded and unfolded conformation. Our results identified hnRNP H/F as important components of the cytoplasmic machinery modulating the structural integrity of RG4s, revealed their function in RG4-mediated translation and uncovered the underlying molecular mechanism impacting the cellular stress response linked to the outcome of glioblastoma. Nature Publishing Group UK 2020-05-27 /pmc/articles/PMC7253433/ /pubmed/32461552 http://dx.doi.org/10.1038/s41467-020-16168-x Text en © The Author(s) 2020, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Herviou, Pauline
Le Bras, Morgane
Dumas, Leïla
Hieblot, Corinne
Gilhodes, Julia
Cioci, Gianluca
Hugnot, Jean-Philippe
Ameadan, Alfred
Guillonneau, François
Dassi, Erik
Cammas, Anne
Millevoi, Stefania
hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma
title hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma
title_full hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma
title_fullStr hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma
title_full_unstemmed hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma
title_short hnRNP H/F drive RNA G-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma
title_sort hnrnp h/f drive rna g-quadruplex-mediated translation linked to genomic instability and therapy resistance in glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253433/
https://www.ncbi.nlm.nih.gov/pubmed/32461552
http://dx.doi.org/10.1038/s41467-020-16168-x
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