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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorJanin, Maxime
dc.contributor.authorOrtiz‑Barahona, Vanessa
dc.contributor.authorCastro de Moura, Manuel
dc.contributor.authorMartínez‑Cardús, Anna
dc.contributor.authorLlinàs‑Arias, Pere
dc.contributor.authorSoler, Marta
dc.contributor.authorArias Piñeiro, Alexandra
dc.contributor.authorCuartas Maza, Ma Isabel
dc.contributor.authorSeoane Suarez, Joan
dc.date.accessioned2021-04-16T11:08:52Z
dc.date.available2021-04-16T11:08:52Z
dc.date.issued2019-12
dc.identifier.citationJanin M, Ortiz-Barahona V, de Moura MC, Martínez-Cardús A, Llinàs-Arias P, Soler M, et al. Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program. Acta Neuropathol. 2019 Dec;138(6):1053–74.
dc.identifier.issn1432-0533
dc.identifier.urihttp://hdl.handle.net/11351/5869
dc.descriptionClinical outcome; Epitranscriptomics; Glioma
dc.description.abstractTumors 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.
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofseriesActa Neuropathologica;138(6)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectGliomes
dc.subjectMetiltransferases
dc.subject.meshGlioma
dc.subject.meshMethyltransferases
dc.titleEpigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1007/s00401-019-02062-4
dc.subject.decsglioma
dc.subject.decsmetiltransferasas
dc.relation.publishversionhttps://link.springer.com/article/10.1007%2Fs00401-019-02062-4
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Janin M, Ortiz-Barahona V, de Moura MC, Martínez-Cardús A, Llinàs-Arias P, Soler M] Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Catalonia, Spain. [Arias A, Cuartas I] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Seoane J] Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain
dc.identifier.pmid31428936
dc.identifier.wos000496124600009
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/FP7/FP7%2F2007-2013
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/SAF2014-55000-R
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F01278
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/PIE13%2F00022
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/CB16%2F12%2F00312
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PERIS2016-2020/2009SGR1315
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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