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Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability

Author

Listed:
  • Katherine L. Harper

    (University of Leeds)

  • Elena M. Harrington

    (University of Leeds)

  • Connor Hayward

    (University of Leeds)

  • Chinedu A. Anene

    (Leeds Beckett University
    Queen Mary University of London)

  • Wiyada Wongwiwat

    (Imperial College London, South Kensington Campus)

  • Robert E. White

    (Imperial College London, South Kensington Campus)

  • Adrian Whitehouse

    (University of Leeds
    Rhodes University)

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.

Suggested Citation

  • Katherine L. Harper & Elena M. Harrington & Connor Hayward & Chinedu A. Anene & Wiyada Wongwiwat & Robert E. White & Adrian Whitehouse, 2024. "Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54592-5
    DOI: 10.1038/s41467-024-54592-5
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    References listed on IDEAS

    as
    1. Michele Vendruscolo & Monika Fuxreiter, 2022. "Protein condensation diseases: therapeutic opportunities," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Laura A. Murray-Nerger & Clarisel Lozano & Eric M. Burton & Yifei Liao & Nathan A. Ungerleider & Rui Guo & Benjamin E. Gewurz, 2024. "The nucleic acid binding protein SFPQ represses EBV lytic reactivation by promoting histone H1 expression," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Dario Dattilo & Gaia Di Timoteo & Adriano Setti & Andrea Giuliani & Giovanna Peruzzi & Manuel Beltran Nebot & Alvaro Centrón-Broco & Davide Mariani & Chiara Mozzetta & Irene Bozzoni, 2023. "The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. James C. Murphy & Elena M. Harrington & Sophie Schumann & Elton J. R. Vasconcelos & Timothy J. Mottram & Katherine L. Harper & Julie L. Aspden & Adrian Whitehouse, 2023. "Kaposi’s sarcoma-associated herpesvirus induces specialised ribosomes to efficiently translate viral lytic mRNAs," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
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