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Cited by 130Viral gastroenteritis research and epidemiologyRNA Research and SplicingVirology and Viral Diseases

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

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Geiger, Florian, Acker, Julia, Papa, Guido, Wang, Xinyu, Arter, William E, Saar, Kadi L, Erkamp, Nadia A, Qi, Runzhang, Bravo, Jack PK, Strauss, Sebastian, Krainer, Georg, Burrone, Oscar R, Jungmann, Ralf, Knowles, Tuomas PJ, Engelke, Hanna, Borodavka, Alexander·2021·The EMBO Journal
DOI 10.15252/embj.2021107711PMC PMC8561643

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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.

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Metadata

Authors
Geiger, F., Acker, J., Papa, G., Wang, X., Arter, W. E., Saar, K. L., Erkamp, N. A., Qi, R., Bravo, J. P., Strauss, S., Krainer, G., Burrone, O. R., Jungmann, R., Knowles, T. P., Engelke, H., & Borodavka, A.
Affiliations
  • Ludwig-Maximilians-Universität München (DE)
  • University of Cambridge (GB)
  • MRC Laboratory of Molecular Biology (GB)
  • Center for NanoScience (DE)
  • University of Graz (AT)
Corresponding author
  • Geiger, Florian
  • Acker, Julia
  • Papa, Guido
  • Wang, Xinyu
  • Borodavka, Alexander
ORCID
Venue
The EMBO Journal
Publisher
Springer Science and Business Media LLC
Published
2021-09-15
Volume
40
Issue
21
Pages
e107711-e107711
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
DOI
10.15252/embj.2021107711
PMC
PMC8561643
OpenAlex
W3200801568
Cited by
130
References
2
Citations by year
2026: 13 · 2025: 20 · 2024: 35 · 2023: 26 · 2022: 24 · 2021: 11
FWCI
7.60
Type
journal article
Language
en
Open access
Licence
Locations
  • The EMBO Journal (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo
  • Apollo (cc-by)
Funders
  • Wellcome Trust (213437/Z/18/Z)
  • Deutsche Forschungsgemeinschaft
Topics
  • Health Sciences › Medicine › Infectious Diseases › Viral gastroenteritis research and epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
rotavirus, replication factories, viroplasm, liquid-liquid phase separation, biomolecular condensates, NSP5, NSP2, 1,6-hexanediol, propylene glycol, viral RNA replication, ribonucleoprotein granules, antiviral agents
MeSH terms
Cytoplasmic Ribonucleoprotein Granules, Animals, Haplorhini, Cattle, Cell Line, Glycols, Humans, Osmolar Concentration, Phosphorylation, Protein Processing, Post-Translational, Rotavirus, Virus Replication, Signal Transduction, Gene Expression Regulation, Viral, RNA-Binding Proteins, Viral Nonstructural Proteins, Genes, Reporter, Virus Assembly, Propylene Glycol, Green Fluorescent Proteins, Host-Pathogen Interactions, HEK293 Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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