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Title: | Epigenetic loss of RNA‑methyltransferase NSUN5 in glioma targets ribosomes to drive stress adaptive translational program |
Author: | Janin, Maxime Ortiz‑Barahona, Vanessa Esteller, Manel Castro de Moura, Manuel Carrato, Cristina Martínez Cardús, Anna Llinàs-Arias, Pere Soler, Marta Nachmani, Daphna Pelletier, Joffrey Schumann, Ulrike Calleja Cervantes, Maria E. Moran, Sebastian Guil, Sonia Bueno Costa, Alberto Piñeyro, David Pérez Salvia, Montserrat Rosselló-Tortella, Margalida Piqué, Laia Bech-Serra, Joan J. Torre Gómez, Carolina de la Vidal-Bel, August Martínez Iniesta, María Martín-Tejera, Juan F. Villanueva Garatachea, Alberto Arias, Alexandra Cuartas, Isabel Aransay, Ana M. Morales La Madrid, Andrés Carcaboso, Ángel M. Santa-Maria Lopez, Vicente Mora Graupera, Jaume Fernández, Agustín F. Fraga, Mario F. Aldecoa Ansórregui, Iban Pedrosa, Leire Graus Ribas, Francesc Martínez Soler, Fina Tortosa i Moreno, Avelina |
Keywords: | Avaluació de resultats (Assistència mèdica) Glioma RNA Metilació Outcome assessment (Medical care) Gliomas RNA Methylation |
Issue Date: | 13-Aug-2019 |
Publisher: | Springer Verlag |
Abstract: | Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease. |
Note: | Reproducció del document publicat a: https://doi.org/10.1007/s00401-019-02062-4 |
It is part of: | Acta Neuropathologica, 2019, vol. 138, num. 6, p. 1053-1074 |
URI: | http://hdl.handle.net/2445/148583 |
Related resource: | https://doi.org/10.1007/s00401-019-02062-4 |
ISSN: | 0001-6322 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Infermeria Fonamental i Clínica) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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