The USP11/TCEAL1 complex promotes transcription elongation to sustain oncogenic gene expression in neuroblastoma
During early transcription, RNA polymerase II (RNAPII) undergoes a series of structural transitions controlled by cyclin-dependent kinases. How protein ubiquitylation and proteasomal degradation control the function of RNAPII is less well understood. Here we show that the deubiquitinating enzyme USP11 forms a complex with TCEAL1, a member of the TFIIS (TCEA)-like protein family. TCEAL1 shares sequence homology with the RNAPII interaction domain of the elongation factor TFIIS (which controls the fate of backtracked RNAPII) and competes with TFIIS for binding to core promoters. USP11 protects TCEAL1 from proteasomal degradation, and TCEAL1 recruits USP11 to RNAPII. Both USP11 and TCEAL1 promote transcription elongation and maintain expression of RPB8, an essential subunit of all three nuclear RNA polymerases. In neuroblastoma, USP11- and TCEAL1-dependent genes define a gene expression program that is characteristic for mesenchymal tumors, which are described as able to escape from many treatments, suggesting that the USP11/TCEAL1 complex promotes transcription elongation to support a critical oncogenic gene expression program.
Authors
- Christina Schülein‐Völk
- Florian Sauer (ORCID: https://orcid.org/0000-0002-2367-9568)
- Carsten Patrick Ade (ORCID: https://orcid.org/0000-0001-7226-1179)
- Petra Beli (ORCID: https://orcid.org/0000-0001-9507-9820)
- Gabriele Büchel (ORCID: https://orcid.org/0000-0001-7070-7341)
- Francesca Conte (ORCID: https://orcid.org/0000-0003-0842-9314)
- Caroline Kisker (ORCID: https://orcid.org/0000-0002-0216-6026)
- Peter Gallant (ORCID: https://orcid.org/0000-0002-8270-5738)
- Seychelle M. Vos (ORCID: https://orcid.org/0000-0003-1985-2994)
- Daniel Fleischhauer
- Giacomo Cossa (ORCID: https://orcid.org/0000-0001-5826-5165)
- Martin Eilers (ORCID: https://orcid.org/0000-0002-0376-6533)
- Raphael Vidal (ORCID: https://orcid.org/0000-0002-4058-2784)
- Rogier Versteeg (ORCID: https://orcid.org/0000-0001-7172-0388)
- Jan Köster (ORCID: https://orcid.org/0000-0002-0890-7585)
- Mareike Müller
- Katrin Trunk
- Steffi Herold
- Markus Dehmer
Institutions
- Howard Hughes Medical Institute (US)
- Johannes Gutenberg University Mainz (DE)
- University of Würzburg (DE)
- Amsterdam UMC Location University of Amsterdam (NL)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Comprehensive Cancer Center Mainfranken (DE)
- Universitätsklinikum Würzburg (DE)
- Massachusetts Institute of Technology (US)
- Charité - Universitätsmedizin Berlin (DE)
- University of Amsterdam (NL)
Publication Details
- Journal
- Genes & Development
- Published
- 2025-04-18
- DOI
- https://doi.org/10.1101/gad.352166.124
- Citations
- 2
- Primary Topic
- Ubiquitin and proteasome pathways
- Type
- article
Funders
- Wilhelm Sander-Stiftung
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe
- Stiftung Charité
- Berlin Institute of Health
- H2020 European Research Council