Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability
Abstract The nucleus is a highly organised yet dynamic environment containing distinct membraneless nuclear bodies. This spatial separation enables a subset of components to be concentrated within biomolecular condensates, allowing efficient and discrete processes to occur which regulate cellular fu...
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| Format: | Article |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54592-5 |
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| author | Katherine L. Harper Elena M. Harrington Connor Hayward Chinedu A. Anene Wiyada Wongwiwat Robert E. White Adrian Whitehouse |
| author_facet | Katherine L. Harper Elena M. Harrington Connor Hayward Chinedu A. Anene Wiyada Wongwiwat Robert E. White Adrian Whitehouse |
| author_sort | Katherine L. Harper |
| collection | DOAJ |
| description | Abstract The nucleus is a highly organised yet dynamic environment containing distinct membraneless nuclear bodies. This spatial separation enables a subset of components to be concentrated within biomolecular condensates, allowing efficient and discrete processes to occur which regulate cellular function. One such nuclear body, paraspeckles, are comprised of multiple paraspeckle proteins (PSPs) built around the architectural RNA, NEAT1_2. Paraspeckle function is yet to be fully elucidated but has been implicated in a variety of developmental and disease scenarios. We demonstrate that Kaposi’s sarcoma-associated herpesvirus (KSHV) drives formation of structurally distinct paraspeckles with a dramatically increased size and altered protein composition that are required for productive lytic replication. We highlight these virus-modified paraspeckles form adjacent to virus replication centres, potentially functioning as RNA processing hubs for viral transcripts during infection. Notably, we reveal that PSP sequestration into virus-modified paraspeckles result in increased genome instability during both KSHV and Epstein Barr virus (EBV) infection, implicating their formation in virus-mediated tumourigenesis. |
| format | Article |
| id | doaj-art-bbc07e1451e846af9302412cbd768d19 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-bbc07e1451e846af9302412cbd768d192025-08-20T02:08:20ZengNature PortfolioNature Communications2041-17232024-11-0115112510.1038/s41467-024-54592-5Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instabilityKatherine L. Harper0Elena M. Harrington1Connor Hayward2Chinedu A. Anene3Wiyada Wongwiwat4Robert E. White5Adrian Whitehouse6School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of LeedsSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of LeedsCentre for Biomedical Science Research, School of Health, Leeds Beckett UniversityDepartment of Infectious Disease, Imperial College London, South Kensington CampusDepartment of Infectious Disease, Imperial College London, South Kensington CampusSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of LeedsAbstract The nucleus is a highly organised yet dynamic environment containing distinct membraneless nuclear bodies. This spatial separation enables a subset of components to be concentrated within biomolecular condensates, allowing efficient and discrete processes to occur which regulate cellular function. One such nuclear body, paraspeckles, are comprised of multiple paraspeckle proteins (PSPs) built around the architectural RNA, NEAT1_2. Paraspeckle function is yet to be fully elucidated but has been implicated in a variety of developmental and disease scenarios. We demonstrate that Kaposi’s sarcoma-associated herpesvirus (KSHV) drives formation of structurally distinct paraspeckles with a dramatically increased size and altered protein composition that are required for productive lytic replication. We highlight these virus-modified paraspeckles form adjacent to virus replication centres, potentially functioning as RNA processing hubs for viral transcripts during infection. Notably, we reveal that PSP sequestration into virus-modified paraspeckles result in increased genome instability during both KSHV and Epstein Barr virus (EBV) infection, implicating their formation in virus-mediated tumourigenesis.https://doi.org/10.1038/s41467-024-54592-5 |
| spellingShingle | Katherine L. Harper Elena M. Harrington Connor Hayward Chinedu A. Anene Wiyada Wongwiwat Robert E. White Adrian Whitehouse Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability Nature Communications |
| title | Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability |
| title_full | Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability |
| title_fullStr | Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability |
| title_full_unstemmed | Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability |
| title_short | Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability |
| title_sort | virus modified paraspeckle like condensates are hubs for viral rna processing and their formation drives genomic instability |
| url | https://doi.org/10.1038/s41467-024-54592-5 |
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