The X-linked trichothiodystrophy-causing gene RNF113A links the spliceosome to cell survival upon DNA damage.

A549 Cells Adenocarcinoma of Lung / genetics Alternative Splicing / genetics Animals Basic Helix-Loop-Helix Transcription Factors / metabolism Cell Nucleus / drug effects Cell Survival / genetics Cisplatin / pharmacology Cytoprotection / drug effects DNA Damage / genetics DNA-Activated Protein Kinase / metabolism DNA-Binding Proteins / deficiency Gene Expression Regulation, Neoplastic / drug effects Genes, X-Linked Humans Introns / genetics Mice, Inbred NOD Mice, SCID Myeloid Cell Leukemia Sequence 1 Protein / metabolism Neoplasm Proteins / metabolism Phosphorylation / drug effects Protein Stability / drug effects Protein Subunits / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism RNA, Messenger / genetics Reactive Oxygen Species / metabolism Spliceosomes / metabolism Trichothiodystrophy Syndromes / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
09 03 2020
Historique:
received: 24 01 2019
accepted: 17 02 2020
entrez: 11 3 2020
pubmed: 11 3 2020
medline: 2 7 2020
Statut: epublish

Résumé

Prolonged cell survival occurs through the expression of specific protein isoforms generated by alternate splicing of mRNA precursors in cancer cells. How alternate splicing regulates tumor development and resistance to targeted therapies in cancer remain poorly understood. Here we show that RNF113A, whose loss-of-function causes the X-linked trichothiodystrophy, is overexpressed in lung cancer and protects from Cisplatin-dependent cell death. RNF113A is a RNA-binding protein which regulates the splicing of multiple candidates involved in cell survival. RNF113A deficiency triggers cell death upon DNA damage through multiple mechanisms, including apoptosis via the destabilization of the prosurvival protein MCL-1, ferroptosis due to enhanced SAT1 expression, and increased production of ROS due to altered Noxa1 expression. RNF113A deficiency circumvents the resistance to Cisplatin and to BCL-2 inhibitors through the destabilization of MCL-1, which thus defines spliceosome inhibitors as a therapeutic approach to treat tumors showing acquired resistance to specific drugs due to MCL-1 stabilization.

Identifiants

DOI: 10.1038/s41467-020-15003-7 PMID: 32152280 PMC: PMC7062854
pubmed: 32152280
doi: 10.1038/s41467-020-15003-7
pii: 10.1038/s41467-020-15003-7
pmc: PMC7062854
doi:

Substances chimiques

Basic Helix-Loop-Helix Transcription Factors 0
DNA-Binding Proteins 0
MCL1 protein, human 0
Myeloid Cell Leukemia Sequence 1 Protein 0
NUPR1 protein, human 0
Neoplasm Proteins 0
PMAIP1 protein, human 0
Protein Subunits 0
Proto-Oncogene Proteins c-bcl-2 0
RNA, Messenger 0
RNF113A protein, human 0
Reactive Oxygen Species 0
DNA-Activated Protein Kinase EC 2.7.11.1
PRKDC protein, human EC 2.7.11.1
Cisplatin Q20Q21Q62J

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1270

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Auteurs

Kateryna Shostak (K)

Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liege, CHU, Sart-Tilman, Liège, Belgium.
Laboratory of Medical Chemistry, University of Liege, CHU, Sart-Tilman, Liège, Belgium.

Zheshen Jiang (Z)

Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liege, CHU, Sart-Tilman, Liège, Belgium.
Laboratory of Medical Chemistry, University of Liege, CHU, Sart-Tilman, Liège, Belgium.

Benoit Charloteaux (B)

Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liege, CHU, Sart-Tilman, Liège, Belgium.
GIGA Genomics Platform, University of Liege, CHU, Sart-Tilman, Liège, Belgium.
Department of Human Genetics, CHU of Liege, University of Liege, Sart-Tilman, 4000, Liège, Belgium.

Alice Mayer (A)

Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liege, CHU, Sart-Tilman, Liège, Belgium.
GIGA Genomics Platform, University of Liege, CHU, Sart-Tilman, Liège, Belgium.

Yvette Habraken (Y)

Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liege, CHU, Sart-Tilman, Liège, Belgium.
Laboratory of Gene Expression and cancer, University of Liege, CHU, Sart-Tilman, Liège, Belgium.

Lars Tharun (L)

Institute for Pathology-University Hospital, Cologne, Germany.

Sebastian Klein (S)

Institute for Pathology-University Hospital, Cologne, Germany.

Xinyi Xu (X)

Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liege, CHU, Sart-Tilman, Liège, Belgium.
Laboratory of Medical Chemistry, University of Liege, CHU, Sart-Tilman, Liège, Belgium.

Hong Quan Duong (HQ)

Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liege, CHU, Sart-Tilman, Liège, Belgium.
Laboratory of Medical Chemistry, University of Liege, CHU, Sart-Tilman, Liège, Belgium.
Center for Molecular Biology, Institute of Research and Development, Duy Tan University, 03 Quang Trung, Danang, Vietnam.

Andrii Vislovukh (A)

Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liege, CHU, Sart-Tilman, Liège, Belgium.
Laboratory of Medical Chemistry, University of Liege, CHU, Sart-Tilman, Liège, Belgium.

Pierre Close (P)

Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liege, CHU, Sart-Tilman, Liège, Belgium.
Laboratory of Cancer Signaling, University of Liege, CHU, Sart-Tilman, Liège, Belgium.
Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Wavres, Belgium.
ORCID: 0000-0002-8844-9616

Alexandra Florin (A)

Institute for Pathology-University Hospital, Cologne, Germany.

Florian Rambow (F)

Laboratory for Molecular Cancer Biology, VIB Center for Cancer Biology and KULeuven, Department of Oncology, 3000, Leuven, Belgium.

Jean-Christophe Marine (JC)

Laboratory for Molecular Cancer Biology, VIB Center for Cancer Biology and KULeuven, Department of Oncology, 3000, Leuven, Belgium.

Reinhard Büttner (R)

Institute for Pathology-University Hospital, Cologne, Germany.

Alain Chariot (A)

Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liege, CHU, Sart-Tilman, Liège, Belgium. Alain.chariot@uliege.be.
Laboratory of Medical Chemistry, University of Liege, CHU, Sart-Tilman, Liège, Belgium. Alain.chariot@uliege.be.
Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Wavres, Belgium. Alain.chariot@uliege.be.

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Classifications MeSH

questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules A549 › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Tumeurs › Tumeurs par siège › Tumeurs du thorax › Adénocarcinome pulmonaire › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Maturation post-transcriptionnelle des ARN › Épissage des ARN › Épissage alternatif › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Eucaryotes › Animaux › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique hélice-boucle-hélice › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Noyau de la cellule › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Survie cellulaire › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Produits chimiques inorganiques › Composés du platine › Cisplatine › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Cytoprotection › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Phénomènes génétiques › Altération de l'ADN › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Protéines liant le poly-adp-ribose › DNA-activated protein kinase › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de liaison à l'ADN › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Phénomènes génétiques › Modes de transmission héréditaire › Gènes liés au chromosome X › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Introns › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée NOD › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris SCID › The X-linked trichothiodystrophy-causing gene...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes c-bcl-2 › Protéine Mcl-1 › The X-linked trichothiodystrophy-causing gene...
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