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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, Andres
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)
Outcome assessment (Medical care)
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:
It is part of: Acta Neuropathologica, 2019, vol. 138, num. 6, p. 1053-1074
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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 (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Infermeria Fonamental i Medicoquirúrgica)

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