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

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 well understood. Here we show that during KSHV infection, kaposin acts in cis as an architectural RNA to rebuild cellular nuclear speckles (NSs) to sites proximal to the viral genome to optimize viral gene expression. We show kaposin RNA is both necessary and sufficient for NS remodelling, and ablating kaposin colocalization 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 define kaposin as an important regulator of KSHV gene expression and, by extension, KSHV-associated disease. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/614208v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@16fb214org.highwire.dtl.DTLVardef@144a0aorg.highwire.dtl.DTLVardef@903b3org.highwire.dtl.DTLVardef@1d1eb26_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe kaposin transcript is the first RNA (cellular or viral) identified as sufficient to scaffold NSs. C_LIO_LIKaposin scaffolding of NSs requires repetitive nucleotide sequences and cellular SRRM2. C_LIO_LILack of kaposin-NS colocalization during KSHV infection impairs viral gene expression. C_LIO_LIKaposin functions in cis to locally influence gene expression. C_LI