Alphavirus infection triggers selective cytoplasmic translocation of nuclear RBPs with moonlighting antiviral roles
RNA is a central molecule for viruses; however, the interactions that viral RNA (vRNA) establishes with the host cell is only starting to be elucidated. Here, we determine the ribonucleoprotein (RNP) composition of the prototypical arthropod-borne Sindbis virus (SINV). We show that SINV RNAs engage with hundreds of cellular proteins, including a group of nuclear RNA-binding proteins (RBPs) with unknown roles in infection. We demonstrate that these nuclear RBPs are selectively translocated to the cytoplasm after infection, where they accumulate in the viral replication organelles (ROs). These nuclear RBPs strongly suppress viral gene expression, with activities spanning viral species and families. Particularly, the U2 small nuclear RNP (snRNP) emerges as an antiviral complex, with both its U2 small nuclear RNA (snRNA) and protein components contributing to the recognition of the vRNA and the antiviral phenotype. These results suggest that the U2 snRNP has RNA-driven antiviral activity in a mechanism reminiscent of the RNAi pathway.
Authors
- Wael Kamel (ORCID: https://orcid.org/0000-0002-7625-2648)
- Eduardo S. Kitano (ORCID: https://orcid.org/0000-0002-5718-7510)
- Aino I. Järvelin (ORCID: https://orcid.org/0000-0002-1225-4396)
- Yana Demyanenko (ORCID: https://orcid.org/0000-0002-6628-1912)
- Marko Noerenberg (ORCID: https://orcid.org/0000-0002-4834-8888)
- Ilan Davis (ORCID: https://orcid.org/0000-0002-5385-3053)
- Zaydah R. de Laurent (ORCID: https://orcid.org/0000-0002-2619-0856)
- Mudimela Madhusudhan
- Manuel García-Moreno (ORCID: https://orcid.org/0000-0001-7181-5459)
- Andres Merits (ORCID: https://orcid.org/0000-0001-8193-0071)
- Alfredo Castelló (ORCID: https://orcid.org/0000-0002-1499-4662)
- Louisa Iselin (ORCID: https://orcid.org/0000-0002-9646-9326)
- Maximilian Hannan
- Shabaz Mohammed (ORCID: https://orcid.org/0000-0003-2640-9560)
- Richard J Orton (ORCID: https://orcid.org/0000-0002-3389-4325)
- Azman Embarc‐Buh (ORCID: https://orcid.org/0000-0002-1980-942X)
- Vincenzo Ruscica (ORCID: https://orcid.org/0000-0003-4082-1893)
- Samantha Moore (ORCID: https://orcid.org/0000-0003-0944-7055)
Institutions
- University of Oxford (GB)
- Medawar Building for Pathogen Research (GB)
- Rosalind Franklin Institute (GB)
- MRC University of Glasgow Centre for Virus Research (GB)
- University of Tartu (EE)
Publication Details
- Journal
- Molecular Cell
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1016/j.molcel.2024.11.015
- Citations
- 15
- Primary Topic
- RNA Research and Splicing
- Type
- article
- Field-Weighted Citation Impact
- 3.51
Funders
- European Commission
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council