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Nuclear body reorganization by the viral RNAkaposinpromotes Kaposi’s sarcoma-associated herpesvirus gene expression

by Mariel Kleer, Michael J. Johnston, and Jennifer A. Corcoran

Posted: September 22, 2024
Server: bioRxiv
DOI: 10.1101/2024.09.20.614208

Summary

Kaposinis the most abundantly expressed viral RNA in tumours caused by the oncogenic virus Kaposi’s sarcoma-associated herpesvirus (KSHV); however, its role in viral replication is not well understood. Here we show that during KSHV infection,kaposinactsin cisas an architectural RNA to rebuild cellular nuclear speckles (NSs) to sites proximal to the viral genome to optimize viral gene expression. We showkaposinRNA is both necessary and sufficient for NS remodelling, and ablatingkaposincolocalization with NSs using kaposin-deficient recombinant viruses impairs viral gene expression. This is the first example of an RNA (cellular or viral) capable of scaffolding NS and the first study to definekaposinas an important regulator of KSHV gene expression and, by extension, KSHV-associated disease.

Highlights

Thekaposintranscript is the first RNA (cellular or viral) identified as sufficient to scaffold NSs.
Kaposinscaffolding of NSs requires repetitive nucleotide sequences and cellular SRRM2.
Lack ofkaposin-NS colocalization during KSHV infection impairs viral gene expression.
Kaposinfunctionsin cisto locally influence gene expression.

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