Nuclear body reorganization by the viral RNA kaposin promotes Kaposi-sarcoma associated herpesvirus gene expression

Kaposin is the most abundantly expressed viral RNA in tumours caused by the oncogenic virus Kaposi-sarcoma associated herpesvirus (KSHV); however, its role in viral replication is not well understood. Here we show that during KSHV infection, kaposin acts as viral architectural RNA which reorganizes cellular nuclear speckles (NS) to sites proximal to the viral genome. We show kaposin is both necessary and sufficient for NS remodelling, making it the first example of an RNA capable of scaffolding NSs. When kaposin does not colocalize with NS, as during infection with kaposin-recombinant viruses, viral gene expression is crippled. Our data demonstrate that KSHV encodes an RNA that functions in cis as a scaffold, leveraging the capability of NS to boost the expression of genes in their proximity. These findings make kaposin an architectural RNA for NSs and an important regulator of KSHV gene expression and critical for KSHV-associated diseases. Overall design: Comparative gene expression analysis between KSHV mutants as well as between latency and 48 hours post-reactivation