We are analyzing https://link.springer.com/article/10.1007/s00401-019-02062-4.

Title:
Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program | Acta Neuropathologica
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.
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Keywords {🔍}

nsun, cells, fig, glioma, cell, pubmed, methylation, rna, suppl, cas, protein, cancer, rrna, google, scholar, lines, translational, epigenetic, human, unmethylated, synthesis, stress, analysis, loss, expression, gliomas, central, test, data, nqo, dbtrgmg, barcelona, hypermethylation, observed, dna, spain, cpg, research, cellular, levels, idh, table, tumors, patients, program, gene, transfection, silencing, status, island,

Topics {✒️}

dna-demethylating agent 5-aza-2-deoxycytidine nsun5-shrna-depleted dbtrg-05mg cells silac-lys8- arg10-kit media nsun5-shrna-depleted dbtrg-05mg demethylating agent 5-aza-2′-deoxycytidine anti-cancer agent isobutyl-deoxynyboquinone respective empty-vector-transfected cells tertiary complex rrna–trna–mrna ln229 empty-vector-transfected cells empty-vector-transfected ln229 cells empty-vector-transfected-derived tumors highly energy-consuming process plvx-ires-zsgreen1 expression plasmid demethylating drug 5-aza-2′-deoxycytidine comparing nsun5 shrna-depleted quantitative real-time pcr real-time quantitative pcr highly energy-demanding process 115 formalin-fixed paraffin-embedded empty-vector-transfected cells high-titer lentiviral particles plvx-shrna2-zsgreen plasmid cotransfecting hek-293t cells parp1-induced programmed necrosis nqo1-activated cancer therapeutics bisulfite rna deep-sequencing empty-vector ln229 cells nsun5-expressing dbtrg-05mg pyrimidine-rich translational sequences resulting bisulfite-modified rna nsun5 shrna-mediated depletion recombinant plvx-ires-zsgreen1 deep-sequencing rna transcriptome thermoscript rt-pcr system nsun5-transfected ln299 cells nsun5 shrna-mediated downregulation x-linked dyskeratosis congenita august vidal eif4a-dependent oncogene translation gene functional-enrichment analysis generalitat de catalunya specific tumor-suppressor role nsun5-transfected ln229 cells nsun5 transfected-ln229 cells stress-mediated translational control stress-response translational program dna-repair gene mgmt c3781-g3810 base pair deletion 1p/19q/mgmt methylation [3h] leucine incorporation

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Gov/object/PRJNA395552?

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WebPage:
      mainEntity:
         headline:Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program
         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.
         datePublished:2019-08-19T00:00:00Z
         dateModified:2019-08-19T00:00:00Z
         pageStart:1053
         pageEnd:1074
         license:http://creativecommons.org/licenses/by/4.0/
         sameAs:https://doi.org/10.1007/s00401-019-02062-4
         keywords:
            Glioma
            Epitranscriptomics
            RNA methylation
            Clinical outcome
            Pathology
            Neurosciences
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         isPartOf:
            name:Acta Neuropathologica
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               1432-0533
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            volumeNumber:138
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                     type:Organization
                     name:Ctra de Can Ruti
                     address:
                        name:Josep Carreras Leukaemia Research Institute (IJC), Ctra de Can Ruti, Badalona, Barcelona, Spain
                        type:PostalAddress
                     type:Organization
               email:[email protected]
               type:Person
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ScholarlyArticle:
      headline:Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program
      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.
      datePublished:2019-08-19T00:00:00Z
      dateModified:2019-08-19T00:00:00Z
      pageStart:1053
      pageEnd:1074
      license:http://creativecommons.org/licenses/by/4.0/
      sameAs:https://doi.org/10.1007/s00401-019-02062-4
      keywords:
         Glioma
         Epitranscriptomics
         RNA methylation
         Clinical outcome
         Pathology
         Neurosciences
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         issn:
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      author:
            name:Maxime Janin
            affiliation:
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                  address:
                     name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
                     type:PostalAddress
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            type:Person
            name:Vanessa Ortiz-Barahona
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                  address:
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                     type:PostalAddress
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            type:Person
            name:Manuel Castro de Moura
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                  address:
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                     type:PostalAddress
                  type:Organization
            type:Person
            name:Anna Martínez-Cardús
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                  address:
                     name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
                     type:PostalAddress
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            name:Pere Llinàs-Arias
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            name:Daphna Nachmani
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                  name:University of Cincinnati Medical School
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            name:Sandra Blanco
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                  name:University of Salamanca
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               name:Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Spain
               type:PostalAddress
            type:Organization
            name:University of Cincinnati Medical School
            address:
               name:Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati Medical School, Cincinnati, USA
               type:PostalAddress
            type:Organization
      name:Sandra Blanco
      affiliation:
            name:CIC bioGUNE
            address:
               name:CIC bioGUNE, Derio, Spain
               type:PostalAddress
            type:Organization
            name:University of Salamanca
            address:
               name:Molecular Mechanisms Program, Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), University of Salamanca, Salamanca, Spain
               type:PostalAddress
            type:Organization
      name:Joan Seoane
      affiliation:
            name:Centro de Investigacion Biomedica en Red Cancer (CIBERONC)
            address:
               name:Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain
               type:PostalAddress
            type:Organization
            name:Universitat Autònoma de Barcelona
            address:
               name:Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
               type:PostalAddress
            type:Organization
            name:Institucio Catalana de Recerca i Estudis Avançats (ICREA)
            address:
               name:Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
               type:PostalAddress
            type:Organization
      name:Thomas Preiss
      affiliation:
            name:The Australian National University
            address:
               name:EMBL-Australia Collaborating Group, Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Acton, Australia
               type:PostalAddress
            type:Organization
            name:Victor Chang Cardiac Research Institute
            address:
               name:Victor Chang Cardiac Research Institute, Darlinghurst (Sydney), Australia
               type:PostalAddress
            type:Organization
      name:Pier Paolo Pandolfi
      affiliation:
            name:Harvard Medical School
            address:
               name:Department of Medicine and Pathology, Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
               type:PostalAddress
            type:Organization
      name:Manel Esteller
      url:http://orcid.org/0000-0003-4490-6093
      affiliation:
            name:L’Hospitalet
            address:
               name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
               type:PostalAddress
            type:Organization
            name:Centro de Investigacion Biomedica en Red Cancer (CIBERONC)
            address:
               name:Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain
               type:PostalAddress
            type:Organization
            name:University of Barcelona
            address:
               name:Department of Biochemistry and Biomedicine, University of Barcelona, Barcelona, Spain
               type:PostalAddress
            type:Organization
            name:Institucio Catalana de Recerca i Estudis Avançats (ICREA)
            address:
               name:Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
               type:PostalAddress
            type:Organization
            name:Ctra de Can Ruti
            address:
               name:Josep Carreras Leukaemia Research Institute (IJC), Ctra de Can Ruti, Badalona, Barcelona, Spain
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Department of Medicine and Pathology, Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
      name:Molecular Mechanisms and Experimental Therapy in Oncology Program, Metabolism and Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:EMBL-Australia Collaborating Group, Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Acton, Australia
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Proteomics Unit, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Proteomics Unit, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Department of Pathology, Hospital Universitari de Bellvitge, IDIBELL, L’Hospitalet del Llobregat, Barcelona, Spain
      name:Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain
      name:Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Oncobell Program, L’Hospitalet del Llobregat, Barcelona, Spain
      name:Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Oncobell Program, L’Hospitalet del Llobregat, Barcelona, Spain
      name:Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Oncobell Program, L’Hospitalet del Llobregat, Barcelona, Spain
      name:Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
      name:Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
      name:Centro de Investigación Bimédica en Red de Enfermedades hepáticas y Digestivas (CIBERehd), CIC bioGUNE, Derio, Spain
      name:Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain
      name:Pediatric Neuro-Oncology Unit, Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain
      name:Preclinical Therapeutics and Drug Delivery Research Program, Fundacio Sant Joan de Deu, Barcelona, Spain
      name:Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain
      name:Pediatric Neuro-Oncology Unit, Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain
      name:Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain
      name:Institute of Oncology of Asturias (IUOPA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA-FINBA), Oviedo, Spain
      name:Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Universidad de Oviedo-Principado de Asturias, Oviedo, Spain
      name:Pathology-Brain Bank, Hospital Clínic de Barcelona-CDB-August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
      name:Glioma and Neural Stem Cell Group and Translational Genomics and Targeted Therapeutics in Solid Tumors Team, IDIBAPS, Barcelona, Spain
      name:Clinical and Experimental Neuroimmunology, IDIBAPS, Barcelona, Spain
      name:Department of Pathology, Hospital Universitari de Bellvitge, IDIBELL, L’Hospitalet del Llobregat, Barcelona, Spain
      name:Faculty of Medicine and Health Sciences-Bellvitge, Universitat de Barcelona, IDIBELL, L’Hospitalet del Llobregat, Barcelona, Spain
      name:Faculty of Medicine and Health Sciences-Bellvitge, Universitat de Barcelona, IDIBELL, L’Hospitalet del Llobregat, Barcelona, Spain
      name:Department of Pathology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain
      name:Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
      name:Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, USA
      name:Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, USA
      name:Institute for Molecular Biosciences, Goethe University, Frankfurt, Germany
      name:Institute for Molecular Biosciences, Goethe University, Frankfurt, Germany
      name:Division of Neuropathology, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
      name:Division of Neuropathology, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
      name:Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada
      name:Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada
      name:Joint IRB-BSC Program on Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
      name:Joint IRB-BSC Program on Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
      name:Department of Biochemistry and Biomedicine, University of Barcelona, Barcelona, Spain
      name:Molecular Mechanisms and Experimental Therapy in Oncology Program, Metabolism and Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Spain
      name:Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati Medical School, Cincinnati, USA
      name:CIC bioGUNE, Derio, Spain
      name:Molecular Mechanisms Program, Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), University of Salamanca, Salamanca, Spain
      name:Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain
      name:Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
      name:Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
      name:EMBL-Australia Collaborating Group, Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Acton, Australia
      name:Victor Chang Cardiac Research Institute, Darlinghurst (Sydney), Australia
      name:Department of Medicine and Pathology, Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
      name:Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet, Barcelona, Spain
      name:Centro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain
      name:Department of Biochemistry and Biomedicine, University of Barcelona, Barcelona, Spain
      name:Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
      name:Josep Carreras Leukaemia Research Institute (IJC), Ctra de Can Ruti, Badalona, Barcelona, Spain

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