TY - JOUR T1 - The Epstein-Barr Virus miR-BHRF1 microRNAs Regulate Viral Gene Expression in <em>cis</em> JF - bioRxiv DO - 10.1101/170746 SP - 170746 AU - Brigid Chiyoko Poling AU - Alexander M. Price AU - Micah A. Luftig AU - Bryan R. Cullen Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/07/31/170746.abstract N2 - The Epstein-Barr virus (EBV) miR-BHRF1 microRNA (miRNA) cluster has been shown to facilitate B-cell transformation and promote the rapid growth of the resultant lymphoblastoid cell lines (LCLs). However, we find that expression of physiological levels of the miR-BHRF1 miRNAs in LCLs transformed with a miR-BHRF1 null mutant (∆123) fails to increase their growth rate. We demonstrate that the pri-miR-BHRF1-2 and 1–3 stem-loops are present in the 3’UTR of transcripts encoding EBNA-LP and that excision of pre-miR-BHRF1-2 and 1–3 by Drosha destabilizes these mRNAs and reduces expression of the encoded protein. Therefore, mutational inactivation of primiR-BHRF1-2 and 1–3 in the ∆123 mutant upregulates the expression of not only EBNA-LP but also EBNA-LP-regulated mRNAs and proteins, including LMP1. We hypothesize that this overexpression causes the reduced transformation capacity of the ∆123 EBV mutant. Thus, in addition to regulating cellular mRNAs in trans, miR-BHRF1-2 and 1–3 also regulate EBNA-LP mRNA expression in cis.HighlightsThe EBV miR-BHRF1 microRNAs do not up upregulate B cell growth in trans.EBNA-LP expression is downregulated by pri-miR-BHRF1-2 and 1–3 acting in cis.Loss of miR-BHRF1-2 and 1–3 causes EBNA-LP overexpression and inhibits B cell growth.Novel alternative splicing of EBV Cp/Wp transcripts was identified. ER -