title: The Epstein-Barr virus microRNA BART11-5p targets the early B-cell transcription factor EBF1.
abstract: Epstein-Barr virus (EBV) is a ubiquitous B-cell trophic herpesvirus associated with a variety of histologically diverse B-cell lymphomas, each associated with specific viral-latency gene expression programs. Initial infection drives resting B-cells to differentiate via an atypical germinal centre reaction into memory B-cells, where the virus resides in a latent state. The mechanisms that underpin this process have yet to be fully elucidated. EBV expresses more than 40 microRNAs (miRNAs). The alternatively spliced BamHI A rightward transcripts (BARTs) are the template for two large miRNA clusters (BARTs A and B), that comprise the majority of all known EBV-miRNAs. Although BART-miRNAs are abundantly expressed in all latency programs, few BART-miRNA targets have been identified and their function is poorly understood. The early B-cell factor 1 (EBF1) was identified using bioinformaticss analysis as a novel target of EBV-miRNA BART11-5p, encoded by BART cluster B. EBF1 is an important B-cell transcription factor that regulates many B-cell specific genes including Pax5, BCR and CD40 and is critical for germinal centre formation. Using luciferase reporter assays and a series of BART-constructs, we confirmed silencing via the EBF1 3' untranslated region (UTR) and identified the target site as 2137-2159 bp after the stop codon. Results were confirmed following transfection of a BART11-5p mimic, which was able to silence via the predicted target site. Our findings highlight a potential role of BART-miRNAs in the regulation of B-cell differentiation.
authors.affiliation: Clinical Immunohematology Laboratory, Queensland Institute of Medical Research Level 10, CBCRC Building, Herston Road, Brisbane, Queensland, 4006 ; Queensland University of Technology 60 Musk Avenue, Kelvin Grove Urban Village, Kelvin Grove, Queensland, 4059, Australia.
authors.forename: Nathan
authors.initials: N
authors.lastname: Ross
authors.forename: Maher K
authors.initials: MK
authors.lastname: Gandhi
authors.forename: Jamie P
authors.initials: JP
authors.lastname: Nourse
keywords: B-cell; BamHI A rightward transcripts; EBV; early B-cell transcription factor; microRNA