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 tumors caused by the oncogenic virus Kaposi’s 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 remodeling, and this effect depends on repetitive elements within the RNA. Absence of kaposin-mediated NS remodeling, depletion of the essential NS protein, serine/arginine repetitive matrix 2 (SRRM2), or steric blocking of the kaposin repetitive elements impair viral gene expression. This work defines kaposin as a viral architectural RNA that drives nuclear speckle seeding beside the viral genome and reframes our understanding of lncRNA function and the spatial organization of transcription in the infected cell nucleus.