Viral miRNA targeting of bicistronic and polycistronic transcripts

•Genome-wide mapping has delineated the features of KSHV transcriptome and 3′UTRs.•Over 30% of KSHV transcripts are bicistronic and polycistronic transcripts.•Viral miRNAs regulate viral life cycle.•KSHV bicistronic and polycistronic transcripts are frequent targets of viral miRNAs.

Successful viral infection entails a choreographic regulation of viral gene expression program. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes numerous miRNAs that regulate viral life cycle. However, few viral targets have been identified due to the lack of information on KSHV 3′ untranslated regions (3′UTRs). Recent genome-wide mapping of KSHV transcripts and 3′UTRs has revealed abundant bicistronic and polycistronic transcripts. The extended 3′UTRs of the 5′ proximal genes of bicistronic and polycistronic transcripts offer additional regulatory targets. Indeed, a genome-wide screening of KSHV 3′UTRs has identified several bicistronic and polycistronic transcripts as the novel targets of viral miRNAs. Together, these works have expanded our knowledge of the unique features of KSHV gene regulation program and provided valuable resources for the research community.