The molecular dissection of TRIM25‘s RNA-binding mechanism provides key insights into its antiviral activity-Reference-Cited by-同舟云学术

The molecular dissection of TRIM25‘s RNA-binding mechanism provides key insights into its antiviral activity

Published:2023-12-11 Issue: Volume: Page:
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Álvarez Lucía¹^ORCID,Haubrich Kevin¹^ORCID,Iselin Louisa²,Gillioz Laurent³^ORCID,Ruscica Vincenzo²^ORCID,Lapouge Karine⁴,Augsten Sandra¹,Huppertz Ina⁵,Choudhury Nila Roy⁶,Simon Bernd⁷,Masiewicz Pawel¹,Lethier Mathilde⁸,Cusack Stephen⁸^ORCID,Rittinger Katrin⁹^ORCID,Gabel Frank¹⁰^ORCID,Leitner Alexander¹¹^ORCID,Michlewski Gracjan⁶^ORCID,Hentze Matthias W.⁵^ORCID,Allain Frédéric H. T.³,Castello Alfredo²^ORCID,Hennig Janosch¹²^ORCID

Affiliation:

1. Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, 69117 Heidelberg, Germany

2. MRC-University of Glasgow Centre for Virus Research, 464 Bearsden Road, Glasgow G61 1QH, Scotland, United Kingdom

3. Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich, Switzerland

4. Protein expression and purification facility, European Molecular Biology Laboratory (EMBL) Heidelberg, 69117 Heidelberg, Germany

5. Director’s Research, European Molecular Biology Laboratory (EMBL) Heidelberg, 69117 Heidelberg, Germany

6. Dioscuri Centre for RNA-Protein Interactions in Human Health and Disease, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland and Infection Medicine, University of Edinburgh, The Chancellor's Building, Edinburgh, United Kingdom

7. Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, 69117 Heidelberg, Germany and Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut, USA

8. European Molecular Biology Laboratory, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France

9. Molecular Structure of Cell Signalling Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, United Kingdom

10. 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, Grenoble, France

11. Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, 8093 Zürich, Switzerland

12. Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, 69117 Heidelberg, Germa and Chair of Biochemistry IV, Biophysical Chemistry, University of Bayreuth, 95447 Bayreuth, Germany

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 and showed that its binding to specific viral RNA regions is critical for its antiviral activity.

Publisher

Research Square Platform LLC

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