Janin, Maxime and Ortiz-Barahona, Vanessa and de Moura, Manuel Castro and Martínez-Cardús, Anna and Llinàs-Arias, Pere and Soler, Marta and Nachmani, Daphna and Pelletier, Joffrey and Schumann, Ulrike and Calleja-Cervantes, Maria E. and Moran, Sebastian and Guil, Sonia and Bueno-Costa, Alberto and Piñeyro, David and Perez-Salvia, Montserrat and Rosselló-Tortella, Margalida and Piqué, Laia and Bech-Serra, Joan J. and De La Torre, Carolina and Vidal, August and Martínez-Iniesta, María and Martín-Tejera, Juan F. and Villanueva, Alberto and Arias, Alexandra and Cuartas, Isabel and Aransay, Ana M. and La Madrid, Andres Morales and Carcaboso, Angel M. and Santa-Maria, Vicente and Mora, Jaume and Fernandez, Agustin F. and Fraga, Mario F. and Aldecoa, Iban and Pedrosa, Leire and Graus, Francesc and Vidal, Noemi and Martínez-Soler, Fina and Tortosa, Avelina and Carrato, Cristina and Balañá, Carme and Boudreau, Matthew W. and Hergenrother, Paul J. and Kötter, Peter and Entian, Karl-Dieter and Hench, Jürgen and Frank, Stephan and Mansouri, Sheila and Zadeh, Gelareh and Dans, Pablo D. and Orozco, Modesto and Thomas, George and Blanco, Sandra and Seoane, Joan and Preiss, Thomas and Pandolfi, Pier Paolo and Esteller, Manel (2019) Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program. Acta Neuropathologica. ISSN 0001-6322
Full text not available from this repository.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.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 11 Oct 2019 00:21 |
| Last Modified: | 11 Oct 2019 00:21 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/857 |
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