Am J Blood Res 2013;3(3):210-224
Original Article
The Epstein-Barr virus microRNA BART11-5p targets the early B-cell
transcription factor EBF1
Nathan Ross, Maher K Gandhi, Jamie P Nourse
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; Department of Haematology, Princess Alexandra Hospital, Ipswich Road, Brisbane,
Queensland, 4102; Centre for Experimental Haematology, West Wing, Translational Research Institute, Southside School of
Medicine, University of Queensland, Princess Alexandra Hospital campus, Ipswich Road, Brisbane, Queensland, 4102
Received April 23, 2013; Accepted May 8, 2013; Epub August 19, 2013; Published August 30, 2013
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. (AJBR1304003).
Keywords: EBV, microRNA, BamHI A rightward transcripts, early B-cell transcription factor, B-cell
Address correspondence to: Dr. Maher K Gandhi, Clinical Immunohematology Laboratory, Queensland Institute of Medical
Research, Level 10, CBCRC Building, Herston Road, Brisbane, Queensland, 4006, Australia. Tel: +61 7 3443 8026; Fax +61 7
3443 7779; E-mail: M.Gandhi@uq.edu.au
Original Article
The Epstein-Barr virus microRNA BART11-5p targets the early B-cell
transcription factor EBF1
Nathan Ross, Maher K Gandhi, Jamie P Nourse
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; Department of Haematology, Princess Alexandra Hospital, Ipswich Road, Brisbane,
Queensland, 4102; Centre for Experimental Haematology, West Wing, Translational Research Institute, Southside School of
Medicine, University of Queensland, Princess Alexandra Hospital campus, Ipswich Road, Brisbane, Queensland, 4102
Received April 23, 2013; Accepted May 8, 2013; Epub August 19, 2013; Published August 30, 2013
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. (AJBR1304003).
Keywords: EBV, microRNA, BamHI A rightward transcripts, early B-cell transcription factor, B-cell
Address correspondence to: Dr. Maher K Gandhi, Clinical Immunohematology Laboratory, Queensland Institute of Medical
Research, Level 10, CBCRC Building, Herston Road, Brisbane, Queensland, 4006, Australia. Tel: +61 7 3443 8026; Fax +61 7
3443 7779; E-mail: M.Gandhi@uq.edu.au
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