Nuclear body assembly by a viral repeat RNA promotes Kaposi's sarcoma-associated herpesvirus gene expression

Abstract

Kaposin is the most abundantly expressed viral RNA in tumours caused by the oncogenic virus Kaposis sarcoma-associated herpesvirus (KSHV); however, its role in viral replication is not understood. Here, we show that kaposin, previously viewed as a protein-coding transcript, exists primarily as a nuclear viral long non-coding RNA (lncRNA) that rebuilds cellular nuclear speckles (NSs) adjacent to the viral genome to enhance viral gene expression. Kaposin is both necessary and sufficient to drive substantial NS remodelling, and this effect depends on repetitive elements within the RNA. Absence of kaposin-mediated NS remodeling, depletion of the essential NS protein, SRRM2, or blocking kaposin repetitive elements with antisense oligonucleotides impairs viral gene expression. Kaposin is the first viral lncRNA discovered to seed a functional nuclear body beside the viral genome. This work reframes our understanding of viral lncRNA function and the spatial organization of transcription in the infected cell nucleus.