Design and characterization of G-quadruplex RNA aptamers reveal RNA-binding by KDM5 lysine demethylases
Here, we show that the histone lysine demethylases KDM5A and KDM5B can bind to RNA through interaction with G-quadruplexes, despite neither being categorized as RNA- nor G-quadruplex binding proteins across numerous experimental large-scale and computational studies. In addition to characterizing the KDM5 G-quadruplex interaction we show that RNA is directly involved in the formation of KDM5-containing protein complexes. Computational predictions and comparisons to other ARID domain containing proteins suggest that the ARID domain is directly interacting with both DNA and RNA across several proteins. Our work highlights that the RNA-binding by KDM5 lysine demethylases is dependent on recognizing G-quadruplex structures and that RNA mediates the formation of alternative KDM5-containing protein complexes.
Authors
- Michael Gajhede (ORCID: https://orcid.org/0000-0001-9864-2287)
- Alexandros Armaos (ORCID: https://orcid.org/0000-0003-0607-5663)
- Johanna Luige (ORCID: https://orcid.org/0000-0003-1314-8103)
- David Meierhofer (ORCID: https://orcid.org/0000-0002-0170-868X)
- Gian Gaetano Tartaglia
- Ulf Andersson Ørom (ORCID: https://orcid.org/0000-0002-0643-0592)
- Thomas Conrad (ORCID: https://orcid.org/0000-0001-5618-6295)
- Anna Vincent
- Annita Louloupi (ORCID: https://orcid.org/0000-0003-3729-9002)
Institutions
- University of Copenhagen (DK)
- Aarhus University (DK)
- Max Delbrück Center (DE)
- Italian Institute of Technology (IT)
- Max Planck Institute for Molecular Genetics (DE)
- Sapienza University of Rome (IT)
Publication Details
- Journal
- Computational and Structural Biotechnology Journal
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1016/j.csbj.2025.06.027
- Citations
- 1
- Primary Topic
- RNA Research and Splicing
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Alexander von Humboldt-Stiftung
- Lundbeckfonden
- Novo Nordisk
- H. Lundbeck A/S