Split genes and their expression in Kaposi's sarcoma-associated herpesvirus.

A split or interrupted gene is defined as a gene consisting of introns and exons. Removal (splicing) of the intron(s) from a primary transcript (pre-mRNA) is essential for creating a mRNA. Initial assignment of a potential protein coding region in the KSHV genome was based on the initiation codon context and predicted protein size larger than 100 amino acids, but the gene discontinuity was disregarded. Experimental investigation of the assigned ORFs has demonstrated that there are up to 25 split genes, more than one fourth of the total KSHV genes described in the KSHV genome. This includes the genes involved in all phases (latent, immediate early, early and late) of KSHV infection. The complexity of a split gene expression depends upon the availability of a proximal promoter and polyadenylation (pA) signal. Sharing a single promoter or a single pA signal by two or three genes is not uncommon in the expression of KSHV split genes and the resulting transcripts are usually polycistronic. Among those of KSHV split genes, 15 genes express a bicistronic or tricistronic RNA and 10 genes express a monocistronic RNA. Alternative RNA splicing could happen in a particular pre-mRNA due to intron or exon inclusion or skipping or the presence of an alternative 5' splice site or 3' splice site. This may, respectively, result in at least 8 species of K8 and 14 species of K15 transcripts. This appears to be related to cell differentiation and stages of the virus infection, presumably involving viral cis elements and trans splicing factors.