Nature Communications (Oct 2024)
The molecular dissection of TRIM25’s RNA-binding mechanism provides key insights into its antiviral activity
- Lucía Álvarez,
- Kevin Haubrich,
- Louisa Iselin,
- Laurent Gillioz,
- Vincenzo Ruscica,
- Karine Lapouge,
- Sandra Augsten,
- Ina Huppertz,
- Nila Roy Choudhury,
- Bernd Simon,
- Pawel Masiewicz,
- Mathilde Lethier,
- Stephen Cusack,
- Katrin Rittinger,
- Frank Gabel,
- Alexander Leitner,
- Gracjan Michlewski,
- Matthias W. Hentze,
- Frédéric H. T. Allain,
- Alfredo Castello,
- Janosch Hennig
Affiliations
- Lucía Álvarez
- Molecular Systems Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg
- Kevin Haubrich
- Molecular Systems Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg
- Louisa Iselin
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford
- Laurent Gillioz
- Institute of Biochemistry, Department of Biology, ETH Zürich
- Vincenzo Ruscica
- MRC-University of Glasgow Centre for Virus Research, 464 Bearsden Road
- Karine Lapouge
- Protein expression and purification facility, European Molecular Biology Laboratory (EMBL) Heidelberg
- Sandra Augsten
- Molecular Systems Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg
- Ina Huppertz
- Director’s Research, European Molecular Biology Laboratory (EMBL) Heidelberg
- Nila Roy Choudhury
- Dioscuri Centre for RNA-Protein Interactions in Human Health and Disease, International Institute of Molecular and Cell Biology in Warsaw
- Bernd Simon
- Molecular Systems Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg
- Pawel Masiewicz
- Molecular Systems Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg
- Mathilde Lethier
- European Molecular Biology Laboratory, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9
- Stephen Cusack
- European Molecular Biology Laboratory, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9
- Katrin Rittinger
- Molecular Structure of Cell Signalling Laboratory, The Francis Crick Institute, 1 Midland Road
- Frank Gabel
- Université Grenoble Alpes, Institut de Biologie Structurale, Grenoble, France; Commissariat à l’Energie Atomique et aux Energies Alternatives, Direction de la Recherche Fondamentale, Institut de Biologie Structurale, Grenoble, France; Centre National de la Recherche Scientifique, Institut de Biologie Structurale
- Alexander Leitner
- Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, 8093
- Gracjan Michlewski
- Dioscuri Centre for RNA-Protein Interactions in Human Health and Disease, International Institute of Molecular and Cell Biology in Warsaw
- Matthias W. Hentze
- Director’s Research, European Molecular Biology Laboratory (EMBL) Heidelberg
- Frédéric H. T. Allain
- Institute of Biochemistry, Department of Biology, ETH Zürich
- Alfredo Castello
- MRC-University of Glasgow Centre for Virus Research, 464 Bearsden Road
- Janosch Hennig
- Molecular Systems Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg
- DOI
- https://doi.org/10.1038/s41467-024-52918-x
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 15
Abstract
Abstract TRIM25 is an RNA-binding ubiquitin E3 ligase with central but poorly understood roles in the innate immune response to RNA viruses. The link between TRIM25’s RNA binding and its role in innate immunity has not been established. Thus, we utilized a multitude of biophysical techniques to identify key RNA-binding residues of TRIM25 and developed an RNA-binding deficient mutant (TRIM25-m9). Using iCLIP2 in virus-infected and uninfected cells, we identified TRIM25’s RNA sequence and structure specificity, that it binds specifically to viral RNA, and that the interaction with RNA is critical for its antiviral activity.
