The Epstein–Barr Virus BART microRNAs target the pro-apoptotic protein Bim

In Epstein–Barr Virus infected epithelial cancers, the alternatively spliced BamHI A rightward transcripts (BARTs) are abundantly expressed and are the template for two large clusters of miRNAs. This study indicates that both of these clusters independently can inhibit apoptosis in response to etoposide in an epithelial cell line. The Bcl-2 interacting mediator of cell death (Bim) was identified using gene expression microarrays and bioinformatic analysis indicated multiple potential binding sites for several BART miRNAs in the Bim 3′UTR. Bim protein was reduced by Cluster I and the individual expression of several miRNAs, while mRNA levels were unaffected. In reporter assays, the Bim 3′ untranslated region (UTR) was inhibited by both clusters but not by any individual miRNAs. These results are consistent with the BART miRNAs downregulating Bim post-transcriptionally in part through the 3′UTR and suggest that there are miRNA recognition sites within other areas of the Bim mRNA.