Virus modified paraspeckles are essential hubs for gene expression and their formation drives genomic instability
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ABSTRACT: The nucleus is a highly organised yet dynamic environment containing distinct membrane nuclear bodies. This spatial separation enables a subset of components to be concentrated within bimolecular 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 essential for productive lytic replication. We highlight these virus-modified paraspeckles form adjacent to virus replication centres, functioning as RNA processing hubs for both viral and cellular transcripts during infection. Notably, we reveal that PSP sequestration into virus-modified paraspeckles results in increased genome instability during both KSHV and Epstein Barr virus (EBV) infection, implicating their formation in virus-mediated tumorigenesis.
ORGANISM(S): Homo sapiens
PROVIDER: GSE277122 | GEO | 2024/11/04
REPOSITORIES: GEO
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