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A thorough screening strategy to identify microRNA targets FREE

Nature Genetics

January 2009

Determining targets for microRNAs (miRNAs) has proved difficult, as bioinformatic approaches tend to identify more potential targets than it is feasible to investigate. Ziegelbauer et al. used a stringent strategy that involved multiple microarray screens to identify mRNA targets of miRNAs encoded by the Kaposi's sarcoma-associated herpesvirus (KSHV). mRNA expression in B cells and endothelial cells was profiled under different conditions of miR-K5 expression or inhibition; identified transcripts were then searched for sequences that matched exactly the 3' UTR of the miRNA seed sequence. Only the BCLAF1 gene met all the criteria necessary to be classified as a target of miR-K5. Further tests revealed that KSHV miR-K9, miR-K10a and miR-K10b also target BCLAF1. When these miRNAs were suppressed in latently infected cells, BCLAF1 expression increased and spontaneous activation of lytic viral replication decreased. The authors suggest that the KSHV miRNAs affecting BCLAF1 act as a switch that facilitates lytic replication in latent cells.