ArticleActa neuropathologica2019
Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program.
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Article in Acta neuropathologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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120citing papers in PubMed
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120 citing papers in PubMed, 191 citations in OpenAlex.
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- RNA modifications in cancer and their detection: a review.Japanese journal of clinical oncology · 2026Review
- Knockdown of 5-methylcytosine RNA methyltransferase NOP2/sun RNA methyltransferase 5 in hepatocellular carcinoma cells affects their biological functions.World journal of gastrointestinal surgery · 2026Article
- Aberrant NSUN1 activity connects mLife science alliance · 2026Article
- NSUN5 and RNA mFrontiers in cell and developmental biology · 2026Review
- Multi-omics characterization of RNA modification enzymes identifies NAT10 as a functionally validated prognostic biomarker in hepatocellular carcinoma.Frontiers in immunology · 2026Article
- NSUNs-driven dysregulation: the next frontier in targeted cancer therapy?Cell death & disease · 2025Review
- Advances in RNA modification in myocardial fibrosis (Review).International journal of molecular medicine · 2025Review
- The Role of NSUN Family Genes in m5C Methylation and Diseases.Biomedicines · 2025Review
- NSUN7-mediated mJournal of translational medicine · 2025Article
- RNA m5C methylation in cancer: mechanisms and biological impact.Oncogenesis · 2025Review
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- NSUN5 Mediates Resistance to Doxorubicin via Up-regulation of DNA Damage Repair Proteins BRCA2 and BRIP1 in Colorectal Cancer.The American journal of pathology · 2025Article
- DNA methylation variations of DNA damage response in glioblastoma: NSUN5 modulates tumor-intrinsic cytosolic DNA-sensing and microglial behavior.Journal of translational medicine · 2025Article
- Epitranscriptomics Regulation of CD70, CD80, and TIGIT in Cancer Immunity.International journal of molecular sciences · 2025Article
- RNA epigenetic modifications as dynamic biomarkers in cancer: from mechanisms to clinical translation.Biomarker research · 2025Review
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60 more citing papers are in PubMed but not listed here.
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Authors and funding
56 authors at 19 institutions in 6 countries.
Maxime JaninCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Vanessa Ortiz-BarahonaCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Manuel Castro de MouraCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Anna Martínez-CardúsCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Pere Llinàs-AriasCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Marta SolerCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Daphna NachmaniDepartment of Medicine and Pathology, Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Joffrey PelletierMolecular Mechanisms and Experimental Therapy in Oncology Program, Metabolism and Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Ulrike SchumannEMBL-Australia Collaborating Group, Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Garran Road, Acton, ACT, 2601, Australia.
Maria E Calleja-CervantesCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Sebastian MoranCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Sonia GuilCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Alberto Bueno-CostaCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
David PiñeyroCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Montserrat Perez-SalviaCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Margalida Rosselló-TortellaCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Laia PiquéCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Joan J Bech-SerraProteomics Unit, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Carolina De La TorreProteomics Unit, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
August VidalDepartment of Pathology, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Catalonia, Spain.
María Martínez-IniestaProgram Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Oncobell Program, L'Hospitalet del Llobregat, Barcelona, Catalonia, Spain.
Juan F Martín-TejeraProgram Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Oncobell Program, L'Hospitalet del Llobregat, Barcelona, Catalonia, Spain.
Alberto VillanuevaProgram Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), Oncobell Program, L'Hospitalet del Llobregat, Barcelona, Catalonia, Spain.
Alexandra AriasVall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
Isabel CuartasVall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
Ana M AransayCentro de Investigación Bimédica en Red de Enfermedades hepáticas y Digestivas (CIBERehd), CIC bioGUNE, 801A Bizkaia Technology Park, 48160, Derio, Spain.
Andres Morales La MadridDepartment of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain.
Angel M CarcabosoPreclinical Therapeutics and Drug Delivery Research Program, Fundacio Sant Joan de Deu, Barcelona, Catalonia, Spain.
Vicente Santa-MariaDepartment of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain.
Jaume MoraDepartment of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Catalonia, Spain.
Agustin F FernandezInstitute of Oncology of Asturias (IUOPA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA-FINBA), 33011, Oviedo, Spain.
Mario F FragaNanomaterials and Nanotechnology Research Center (CINN-CSIC), Universidad de Oviedo-Principado de Asturias, Oviedo, Spain.
Iban AldecoaPathology-Brain Bank, Hospital Clínic de Barcelona-CDB-August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Catalonia, Spain.
Leire PedrosaGlioma and Neural Stem Cell Group and Translational Genomics and Targeted Therapeutics in Solid Tumors Team, IDIBAPS, Barcelona, Catalonia, Spain.
Francesc GrausClinical and Experimental Neuroimmunology, IDIBAPS, Barcelona, Catalonia, Spain.
Noemi VidalDepartment of Pathology, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Catalonia, Spain.
Fina Martínez-SolerFaculty of Medicine and Health Sciences-Bellvitge, Universitat de Barcelona, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Catalonia, Spain.
Avelina TortosaFaculty of Medicine and Health Sciences-Bellvitge, Universitat de Barcelona, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Catalonia, Spain.
Cristina CarratoDepartment of Pathology, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain.
Carme BalañáCatalan Institute of Oncology, Hospital Germans Trias i Pujol, 08916, Badalona, Barcelona, Catalonia, Spain.
Matthew W BoudreauDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Paul J HergenrotherDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Peter KötterInstitute for Molecular Biosciences, Goethe University, Frankfurt, Germany.
Karl-Dieter EntianInstitute for Molecular Biosciences, Goethe University, Frankfurt, Germany.
Jürgen HenchDivision of Neuropathology, Institute of Medical Genetics and Pathology, University Hospital Basel, 4031, Basel, Switzerland.
Stephan FrankDivision of Neuropathology, Institute of Medical Genetics and Pathology, University Hospital Basel, 4031, Basel, Switzerland.
Sheila MansouriDivision of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.
Gelareh ZadehDivision of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.
Pablo D DansJoint IRB-BSC Program on Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028, Barcelona, Catalonia, Spain.
Modesto OrozcoJoint IRB-BSC Program on Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028, Barcelona, Catalonia, Spain.
George ThomasMolecular Mechanisms and Experimental Therapy in Oncology Program, Metabolism and Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain.
Sandra BlancoCIC bioGUNE, 801A Bizkaia Technology Park, 48160, Derio, Spain.
Joan SeoaneCentro de Investigacion Biomedica en Red Cancer (CIBERONC), Madrid, Spain.
Thomas PreissEMBL-Australia Collaborating Group, Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Garran Road, Acton, ACT, 2601, Australia.
Pier Paolo PandolfiDepartment of Medicine and Pathology, Cancer Research Institute, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Manel EstellerCancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Catalonia, Spain. mesteller@carrerasresearch.org.ORCID 0000-0003-4490-6093
Institut d'Investigació Biomédica de Bellvitge · ESBellvitge University Hospital · ESHospital Sant Joan de Déu Barcelona · ESUniversitat Autònoma de Barcelona · ESAustralian National University · AUBeth Israel Deaconess Medical Center · USCIC bioGUNE · ESConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESGoethe University Frankfurt · DEInstitució Catalana de Recerca i Estudis Avançats · ESInstitute for Research in Biomedicine · ESUniversity Hospital of Basel · CHUniversity of Illinois Urbana-Champaign · USUniversity of Toronto · CAHospital Clínic de Barcelona · ESInstitut Català d'Oncologia · ESInstituto de Investigación Sanitaria del Principado de Asturias · ESSant Joan de Déu Research Foundation · ESUniversidad de Oviedo · ES
Funding
Training Program in Chemistry-Interface with BiologyT32GM070421 · NIGMS · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI HERGENROTHER, PAUL · 2005 to 2019
$5.4MTraining Program at the Chemistry Biology InterfaceT32GM136629 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Paul Hergenrother · 2020 to 2026
$4.5MMinisterio de Economía y Competitividad SAF2014-55000-RNIGMS NIH HHS T32 GM070421NIGMS NIH HHS T32 GM136629
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.
Indexed as
Epigenesis, GeneticAnimalsBiomarkers, TumorBrain NeoplasmsCell Line, TumorDNA MethylationGliomaHumansMethyltransferasesMice, NudeMuscle ProteinsNeoplasm TransplantationProtein BiosynthesisRibosomesRNA, Ribosomal, 28SBiomarkers, TumorMethyltransferasesMuscle ProteinsNSUN5 protein, humanRNA, Ribosomal, 28SClinical outcomeEpitranscriptomicsGliomaRNA methylation
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