Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses
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Authors
Geiger, Florian
Acker, Julia
Papa, Guido
Wang, Xinyu
Arter, William E
Saar, Kadi L
Erkamp, Nadia
Qi, Runzhang
Bravo, Jack
Strauss, Sebastian
Burrone, Oscar R
Jungmann, Ralf
Knowles, Tuomas PJ
Engelke, Hanna
Publication Date
2021-11-02Journal Title
The EMBO Journal
ISSN
0261-4189
Publisher
EMBO Press
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Geiger, F., Acker, J., Papa, G., Wang, X., Arter, W. E., Saar, K. L., Erkamp, N., et al. (2021). Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. The EMBO Journal https://doi.org/10.15252/embj.2021107711
Abstract
RNA viruses induce the formation of subcellular organelles that
provide microenvironments conducive to their replication. Here we
show that replication factories of rotaviruses represent proteinRNA condensates that are formed via liquid–liquid phase separation of the viroplasm-forming proteins NSP5 and rotavirus RNA chaperone NSP2. Upon mixing, these proteins readily form condensates at physiologically relevant low micromolar concentrations achieved in the cytoplasm of virus-infected cells. Early infection stage condensates could be reversibly dissolved by 1,6-hexanediol, as well as propylene glycol that released rotavirus transcripts from these condensates. During the early stages of infection, propylene
glycol treatments reduced viral replication and phosphorylation of
the condensate-forming protein NSP5. During late infection, these
condensates exhibited altered material properties and became
resistant to propylene glycol, coinciding with hyperphosphorylation of NSP5. Some aspects of the assembly of cytoplasmic rotavirus replication factories mirror the formation of other ribonucleoprotein granules. Such viral RNA-rich condensates that support replication of multi-segmented genomes represent an attractive target for developing novel therapeutic approaches.
Sponsorship
European Research Council (337969)
European Commission Horizon 2020 (H2020) Future and Emerging Technologies (FET) (766972)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (841466)
Identifiers
External DOI: https://doi.org/10.15252/embj.2021107711
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330715
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