Intragenic recruitment of NF-κB drives splicing modifications upon activation by the oncogene Tax of HTLV-1

Lamya Ben Ameur, Paul Marie, Morgan Thenoz, Guillaume Giraud, Emmanuel Combe, Jean-Baptiste Claude, Sebastien Lemaire, Nicolas Fontrodona, Hélène Polveche, Marine Bastien, Antoine Gessain, Eric Wattel, Cyril F. Bourgeois, Didier Auboeuf () and Franck Mortreux ()
Additional contact information
Lamya Ben Ameur: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210
Paul Marie: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210
Morgan Thenoz: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210
Guillaume Giraud: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210
Emmanuel Combe: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210
Jean-Baptiste Claude: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210
Sebastien Lemaire: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210
Nicolas Fontrodona: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210
Hélène Polveche: CECS, I-Stem
Marine Bastien: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210
Antoine Gessain: Unité dʼEpidémiologie et Physiopathologie des Virus Oncogénes, Institut Pasteur
Eric Wattel: Université Lyon 1, CNRS UMR5239, Oncovirologie et Biothérapies, Faculté de Médecine Lyon Sud, ENS - HCL
Cyril F. Bourgeois: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210
Didier Auboeuf: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210
Franck Mortreux: Univ Lyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Chronic NF-κB activation in inflammation and cancer has long been linked to persistent activation of NF-κB–responsive gene promoters. However, NF-κB factors also massively bind to gene bodies. Here, we demonstrate that recruitment of the NF-κB factor RELA to intragenic regions regulates alternative splicing upon NF-κB activation by the viral oncogene Tax of HTLV-1. Integrative analyses of RNA splicing and chromatin occupancy, combined with chromatin tethering assays, demonstrate that DNA-bound RELA interacts with and recruits the splicing regulator DDX17, in an NF-κB activation-dependent manner. This leads to alternative splicing of target exons due to the RNA helicase activity of DDX17. Similar results were obtained upon Tax-independent NF-κB activation, indicating that Tax likely exacerbates a physiological process where RELA provides splice target specificity. Collectively, our results demonstrate a physical and direct involvement of NF-κB in alternative splicing regulation, which significantly revisits our knowledge of HTLV-1 pathogenesis and other NF-κB-related diseases.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-16853-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16853-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-16853-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().