Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses

Geiger F, Acker J, Papa G, Wang X, Arter WE, Saar KL, Erkamp NA, Qi R, Bravo JPK, Strauss S, Krainer G, Burrone OR, Jungmann R, Knowles TP, Engelke H, Borodavka A. 2021. Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. The EMBO Journal. 40(21), e107711.

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Author
Geiger, Florian; Acker, Julia; Papa, Guido; Wang, Xinyu; Arter, William E; Saar, Kadi L; Erkamp, Nadia A; Qi, Runzhang; Bravo, JackISTA ; Strauss, Sebastian; Krainer, Georg; Burrone, Oscar R
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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 protein‐RNA 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.
Publishing Year
Date Published
2021-11-02
Journal Title
The EMBO Journal
Volume
40
Issue
21
Article Number
e107711
ISSN
eISSN
IST-REx-ID

Cite this

Geiger F, Acker J, Papa G, et al. Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. The EMBO Journal. 2021;40(21). doi:10.15252/embj.2021107711
Geiger, F., Acker, J., Papa, G., Wang, X., Arter, W. E., Saar, K. L., … Borodavka, A. (2021). Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. The EMBO Journal. Embo Press. https://doi.org/10.15252/embj.2021107711
Geiger, Florian, Julia Acker, Guido Papa, Xinyu Wang, William E Arter, Kadi L Saar, Nadia A Erkamp, et al. “Liquid–Liquid Phase Separation Underpins the Formation of Replication Factories in Rotaviruses.” The EMBO Journal. Embo Press, 2021. https://doi.org/10.15252/embj.2021107711.
F. Geiger et al., “Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses,” The EMBO Journal, vol. 40, no. 21. Embo Press, 2021.
Geiger F, Acker J, Papa G, Wang X, Arter WE, Saar KL, Erkamp NA, Qi R, Bravo JPK, Strauss S, Krainer G, Burrone OR, Jungmann R, Knowles TP, Engelke H, Borodavka A. 2021. Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. The EMBO Journal. 40(21), e107711.
Geiger, Florian, et al. “Liquid–Liquid Phase Separation Underpins the Formation of Replication Factories in Rotaviruses.” The EMBO Journal, vol. 40, no. 21, e107711, Embo Press, 2021, doi:10.15252/embj.2021107711.
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