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 pri-miR-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.

爱泼斯坦-巴尔病毒（EBV）miR-BHRF1 microRNA（miRNA）簇已显示出促进B细胞转化并促进所得淋巴母细胞样细胞系（LCL）的快速生长。但是，我们发现，在用miR-BHRF1无效突变体（∆123）转化的LCL中，miR-BHRF1 miRNA的生理水平表达无法提高其生长速度。我们证明了pri-miR-BHRF1-2和1-3茎环存在于编码EBNA-LP的转录物的3'UTR中，Drosha切除pre-miR-BHRF1-2和1-3使这些不稳定mRNA和降低编码蛋白的表达。因此，∆123突变体中pri-miR-BHRF1-2和1-3的突变失活不仅上调EBNA-LP的表达，而且上调EBNA-LP调节的mRNA和蛋白质，包括LMP1。我们假设这种过表达会导致Δ123EBV突变体的转化能力降低。因此，除了调节细胞内的mRNA反式，miR-BHRF1-2和1-3也调节顺式EBNA-LP mRNA的表达。