Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program
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-associ...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:223379 |
| Acceso en línea: | https://ddd.uab.cat/record/223379 https://dx.doi.org/urn:doi:10.1007/s00401-019-02062-4 |
| Access Level: | acceso abierto |
| Palabra clave: | Glioma Epitranscriptomics RNA methylation Clinical outcome |
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oai:ddd.uab.cat:223379 |
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España |
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| dc.title.none.fl_str_mv |
Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program |
| title |
Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program |
| spellingShingle |
Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program Janin, Maxime|||0000-0003-1013-4128 Glioma Epitranscriptomics RNA methylation Clinical outcome |
| title_short |
Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program |
| title_full |
Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program |
| title_fullStr |
Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program |
| title_full_unstemmed |
Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program |
| title_sort |
Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program |
| dc.creator.none.fl_str_mv |
Janin, Maxime|||0000-0003-1013-4128 Ortiz-Barahona, V. de Moura, M. C. Martínez Cardús, Anna|||0000-0002-3937-8794 Llinàs-Arias, Pere|||0000-0002-3666-0532 Soler, Marta|||0000-0002-6656-957X Nachmani, D. Pelletier, Joffrey|||0000-0001-9174-044X Schumann, U. Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793 Moran, S.|||0000-0003-4192-8983 Guil, Sonia|||0000-0002-2257-3331 Bueno-Costa, Alberto|||0000-0001-8700-2540 Piñeyro, David|||0000-0001-5633-3339 Perez-Salvia, Montserrat Rosselló-Tortella, M. Piqué, Laia Bech-Serra, Joan-Josep|||0000-0003-3486-781X De La Torre Gómez, Gisela Carolina|||0000-0001-9363-291X Vidal, August|||0000-0001-5727-2099 Martínez-Iniesta, M. Martín-Tejera, J. F. Villanueva, Alejandro|||0000-0001-5164-0006 Arias, Alexandra Cuartas, Isabel Aransay, Ana M.|||0000-0002-8271-612X La Madrid, A. M. Carcaboso, Angel M.|||0000-0002-8485-426X Santa-Maria, V. Mora, J. Fernández, Agustín F.|||0000-0002-3792-4085 Fraga, M. F. Aldecoa, Iban|||0000-0001-5774-7453 Pedrosa, Leire|||0000-0002-1852-4975 Graus Ribas, Francesc|||0000-0002-8924-8322 Vidal, Noemí|||0000-0002-2852-6667 Martinez, Fina|||0000-0002-0940-1025 Tortosa, Avelina|||0000-0002-9080-2976 Carrato, Cristina|||0000-0002-1953-8287 Balañá, Carmen|||0000-0003-0771-0390 Boudreau, M. W. Hergenrother, P. J. Kötter, P. Entian, K. D. Hench, Jürgen Frank, Stephan|||0000-0001-6165-0187 Mansouri, S. Zadeh, G. Dans, P. D. Orozco López, Modesto|||0000-0002-8608-3278 Thomas, Gareth J. Blanco, Sandra Seoane Suárez, Joan|||0000-0002-6541-5974 Preiss, T. Pandolfi, P. P. Esteller, M.|||0000-0003-4490-6093 |
| author |
Janin, Maxime|||0000-0003-1013-4128 |
| author_facet |
Janin, Maxime|||0000-0003-1013-4128 Ortiz-Barahona, V. de Moura, M. C. Martínez Cardús, Anna|||0000-0002-3937-8794 Llinàs-Arias, Pere|||0000-0002-3666-0532 Soler, Marta|||0000-0002-6656-957X Nachmani, D. Pelletier, Joffrey|||0000-0001-9174-044X Schumann, U. Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793 Moran, S.|||0000-0003-4192-8983 Guil, Sonia|||0000-0002-2257-3331 Bueno-Costa, Alberto|||0000-0001-8700-2540 Piñeyro, David|||0000-0001-5633-3339 Perez-Salvia, Montserrat Rosselló-Tortella, M. Piqué, Laia Bech-Serra, Joan-Josep|||0000-0003-3486-781X De La Torre Gómez, Gisela Carolina|||0000-0001-9363-291X Vidal, August|||0000-0001-5727-2099 Martínez-Iniesta, M. Martín-Tejera, J. F. Villanueva, Alejandro|||0000-0001-5164-0006 Arias, Alexandra Cuartas, Isabel Aransay, Ana M.|||0000-0002-8271-612X La Madrid, A. M. Carcaboso, Angel M.|||0000-0002-8485-426X Santa-Maria, V. Mora, J. Fernández, Agustín F.|||0000-0002-3792-4085 Fraga, M. F. Aldecoa, Iban|||0000-0001-5774-7453 Pedrosa, Leire|||0000-0002-1852-4975 Graus Ribas, Francesc|||0000-0002-8924-8322 Vidal, Noemí|||0000-0002-2852-6667 Martinez, Fina|||0000-0002-0940-1025 Tortosa, Avelina|||0000-0002-9080-2976 Carrato, Cristina|||0000-0002-1953-8287 Balañá, Carmen|||0000-0003-0771-0390 Boudreau, M. W. Hergenrother, P. J. Kötter, P. Entian, K. D. Hench, Jürgen Frank, Stephan|||0000-0001-6165-0187 Mansouri, S. Zadeh, G. Dans, P. D. Orozco López, Modesto|||0000-0002-8608-3278 Thomas, Gareth J. Blanco, Sandra Seoane Suárez, Joan|||0000-0002-6541-5974 Preiss, T. Pandolfi, P. P. Esteller, M.|||0000-0003-4490-6093 |
| author_role |
author |
| author2 |
Ortiz-Barahona, V. de Moura, M. C. Martínez Cardús, Anna|||0000-0002-3937-8794 Llinàs-Arias, Pere|||0000-0002-3666-0532 Soler, Marta|||0000-0002-6656-957X Nachmani, D. Pelletier, Joffrey|||0000-0001-9174-044X Schumann, U. Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793 Moran, S.|||0000-0003-4192-8983 Guil, Sonia|||0000-0002-2257-3331 Bueno-Costa, Alberto|||0000-0001-8700-2540 Piñeyro, David|||0000-0001-5633-3339 Perez-Salvia, Montserrat Rosselló-Tortella, M. Piqué, Laia Bech-Serra, Joan-Josep|||0000-0003-3486-781X De La Torre Gómez, Gisela Carolina|||0000-0001-9363-291X Vidal, August|||0000-0001-5727-2099 Martínez-Iniesta, M. Martín-Tejera, J. F. Villanueva, Alejandro|||0000-0001-5164-0006 Arias, Alexandra Cuartas, Isabel Aransay, Ana M.|||0000-0002-8271-612X La Madrid, A. M. Carcaboso, Angel M.|||0000-0002-8485-426X Santa-Maria, V. Mora, J. Fernández, Agustín F.|||0000-0002-3792-4085 Fraga, M. F. Aldecoa, Iban|||0000-0001-5774-7453 Pedrosa, Leire|||0000-0002-1852-4975 Graus Ribas, Francesc|||0000-0002-8924-8322 Vidal, Noemí|||0000-0002-2852-6667 Martinez, Fina|||0000-0002-0940-1025 Tortosa, Avelina|||0000-0002-9080-2976 Carrato, Cristina|||0000-0002-1953-8287 Balañá, Carmen|||0000-0003-0771-0390 Boudreau, M. W. Hergenrother, P. J. Kötter, P. Entian, K. D. Hench, Jürgen Frank, Stephan|||0000-0001-6165-0187 Mansouri, S. Zadeh, G. Dans, P. D. Orozco López, Modesto|||0000-0002-8608-3278 Thomas, Gareth J. Blanco, Sandra Seoane Suárez, Joan|||0000-0002-6541-5974 Preiss, T. Pandolfi, P. P. Esteller, M.|||0000-0003-4490-6093 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Glioma Epitranscriptomics RNA methylation Clinical outcome |
| topic |
Glioma Epitranscriptomics RNA methylation Clinical outcome |
| description |
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. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2 2019-01-01 2019 2019-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/223379 https://dx.doi.org/urn:doi:10.1007/s00401-019-02062-4 |
| url |
https://ddd.uab.cat/record/223379 https://dx.doi.org/urn:doi:10.1007/s00401-019-02062-4 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
European Commission https://doi.org/10.13039/501100000780 268626 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2014-55000-R Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PIE13-00022 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI16-01278 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CB1-12-00312 Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PT13-0010-0009 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2009/SGR-1315 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-633 |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Dipòsit Digital de Documents de la UAB |
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1869422172676554752 |
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Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational programJanin, Maxime|||0000-0003-1013-4128Ortiz-Barahona, V.de Moura, M. C.Martínez Cardús, Anna|||0000-0002-3937-8794Llinàs-Arias, Pere|||0000-0002-3666-0532Soler, Marta|||0000-0002-6656-957XNachmani, D.Pelletier, Joffrey|||0000-0001-9174-044XSchumann, U.Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793Moran, S.|||0000-0003-4192-8983Guil, Sonia|||0000-0002-2257-3331Bueno-Costa, Alberto|||0000-0001-8700-2540Piñeyro, David|||0000-0001-5633-3339Perez-Salvia, MontserratRosselló-Tortella, M.Piqué, LaiaBech-Serra, Joan-Josep|||0000-0003-3486-781XDe La Torre Gómez, Gisela Carolina|||0000-0001-9363-291XVidal, August|||0000-0001-5727-2099Martínez-Iniesta, M.Martín-Tejera, J. F.Villanueva, Alejandro|||0000-0001-5164-0006Arias, AlexandraCuartas, IsabelAransay, Ana M.|||0000-0002-8271-612XLa Madrid, A. M.Carcaboso, Angel M.|||0000-0002-8485-426XSanta-Maria, V.Mora, J.Fernández, Agustín F.|||0000-0002-3792-4085Fraga, M. F.Aldecoa, Iban|||0000-0001-5774-7453Pedrosa, Leire|||0000-0002-1852-4975Graus Ribas, Francesc|||0000-0002-8924-8322Vidal, Noemí|||0000-0002-2852-6667Martinez, Fina|||0000-0002-0940-1025Tortosa, Avelina|||0000-0002-9080-2976Carrato, Cristina|||0000-0002-1953-8287Balañá, Carmen|||0000-0003-0771-0390Boudreau, M. W.Hergenrother, P. J.Kötter, P.Entian, K. D.Hench, JürgenFrank, Stephan|||0000-0001-6165-0187Mansouri, S.Zadeh, G.Dans, P. D.Orozco López, Modesto|||0000-0002-8608-3278Thomas, Gareth J.Blanco, SandraSeoane Suárez, Joan|||0000-0002-6541-5974Preiss, T.Pandolfi, P. P.Esteller, M.|||0000-0003-4490-6093GliomaEpitranscriptomicsRNA methylationClinical outcomeTumors 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.Universitat Autònoma de Barcelona 22019-01-0120192019-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/223379https://dx.doi.org/urn:doi:10.1007/s00401-019-02062-4reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengEuropean Commission https://doi.org/10.13039/501100000780 268626Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2014-55000-RInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PIE13-00022Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI16-01278Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CB1-12-00312Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PT13-0010-0009Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2009/SGR-1315Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-633open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2233792026-06-06T12:50:31Z |
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15,198674 |