Article (Scientific journals)
The X-linked trichothiodystrophy-causing gene RNF113A links the spliceosome to cell survival upon DNA damage
Shostak, Kateryna; Jiang, Zheshen; CHARLOTEAUX, Benoit et al.
2020In Nature Communications, 11 (1)
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Keywords :
Lung cancer; Spliceosome; new therapy
Abstract :
[en] Prolonged cell survival occur 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.
Research center :
GIGA Stem Cells
Disciplines :
Author, co-author :
Shostak, Kateryna ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Jiang, Zheshen ;  Université de Liège - ULiège > Cardiovascular Sciences-Cardiology
CHARLOTEAUX, Benoit ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Service de génétique
Mayer, Alice  ;  Université de Liège - ULiège > Platform Genomics
Habraken, Yvette ;  Université de Liège - ULiège > Molecular Biology of Diseases-Gene Expression & Cancer
Tharun, Lars
Klein, Sebastian
Xu, Xinyi
Duong, Hong Quan 
Vislovukh, Andrii
Close, Pierre  ;  Université de Liège - ULiège > Stem Cells-Cancer Signaling
Florin, Alexandra
Rambow, Florian
Marine, Jean-Christophe
Büttner, Reinhard
Chariot, Alain ;  Université de Liège - ULiège > Stem Cells-Medical Chemistry
More authors (6 more) Less
Language :
Title :
The X-linked trichothiodystrophy-causing gene RNF113A links the spliceosome to cell survival upon DNA damage
Publication date :
09 March 2020
Journal title :
Nature Communications
Publisher :
Nature Publishing Group, United Kingdom
Volume :
Issue :
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
WELBIO - Walloon Excellence in Life Sciences and Biotechnology [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Télévie [BE]
Fondation contre le Cancer [BE]
Fonds Léon Fredericq [BE]
ULiège - Université de Liège [BE]
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