Liquid-liquid phase separation underpins the formation of replication factories in rotaviruses
© 2021 The Authors. Published under the terms of the CC BY 4.0 license..
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.
| Errataetall: |
CommentIn: EMBO J. 2021 Nov 2;40(21):e109558. - PMID 34569635 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
The EMBO journal - 40(2021), 21 vom: 02. Nov., Seite e107711 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Geiger, Florian [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.12.2021 Date Revised 04.04.2024 published: Print-Electronic CommentIn: EMBO J. 2021 Nov 2;40(21):e109558. - PMID 34569635 Citation Status MEDLINE |
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| doi: |
10.15252/embj.2021107711 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM330667637 |
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| 245 | 1 | 0 | |a Liquid-liquid phase separation underpins the formation of replication factories in rotaviruses |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 14.12.2021 | ||
| 500 | |a Date Revised 04.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: EMBO J. 2021 Nov 2;40(21):e109558. - PMID 34569635 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. Published under the terms of the CC BY 4.0 license. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a RNP granules | |
| 650 | 4 | |a biomolecular condensates | |
| 650 | 4 | |a microfluidics | |
| 650 | 4 | |a viral genome assembly | |
| 650 | 7 | |a Glycols |2 NLM | |
| 650 | 7 | |a NSP5 protein, rotavirus group A |2 NLM | |
| 650 | 7 | |a RNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a Viral Nonstructural Proteins |2 NLM | |
| 650 | 7 | |a enhanced green fluorescent protein |2 NLM | |
| 650 | 7 | |a NS35 protein, rotavirus |2 NLM | |
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| 700 | 1 | |a Acker, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Papa, Guido |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Arter, William E |e verfasserin |4 aut | |
| 700 | 1 | |a Saar, Kadi L |e verfasserin |4 aut | |
| 700 | 1 | |a Erkamp, Nadia A |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Runzhang |e verfasserin |4 aut | |
| 700 | 1 | |a Bravo, Jack Pk |e verfasserin |4 aut | |
| 700 | 1 | |a Strauss, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Krainer, Georg |e verfasserin |4 aut | |
| 700 | 1 | |a Burrone, Oscar R |e verfasserin |4 aut | |
| 700 | 1 | |a Jungmann, Ralf |e verfasserin |4 aut | |
| 700 | 1 | |a Knowles, Tuomas Pj |e verfasserin |4 aut | |
| 700 | 1 | |a Engelke, Hanna |e verfasserin |4 aut | |
| 700 | 1 | |a Borodavka, Alexander |e verfasserin |4 aut | |
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