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

Aron R Marquitz1, Anuja Mathur, Cyd Stacy Nam

  • 1Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. arm6@med.unc.edu

Virology
|February 22, 2011
PubMed

Insights

Epstein-Barr Virus (EBV) BART miRNAs inhibit apoptosis by downregulating Bim protein post-transcriptionally. These microRNAs target Bim mRNA, reducing its protein levels without affecting mRNA quantity in epithelial cancer cells.

Area of Science:

  • Molecular Biology
  • Virology
  • Cancer Research

Background:

  • Epstein-Barr Virus (EBV) is associated with epithelial cancers.
  • Alternatively spliced BamHI A rightward transcripts (BARTs) are highly expressed in EBV-infected cells.
  • BARTs serve as precursors for microRNA (miRNA) clusters that regulate cellular processes.

Purpose of the Study:

  • To investigate the role of BART miRNA clusters in regulating apoptosis in epithelial cancer cells.
  • To identify the molecular targets of BART miRNAs involved in apoptosis.
  • To elucidate the mechanism of BART miRNA-mediated gene regulation.

Main Methods:

  • Gene expression microarrays to identify potential targets.
  • Bioinformatic analysis to predict miRNA binding sites.
  • Reporter assays to validate miRNA-target interactions.
  • Western blotting to assess protein level changes.

Main Results:

  • Both BART miRNA clusters independently inhibited etoposide-induced apoptosis.
  • The Bcl-2 interacting mediator of cell death (Bim) was identified as a target.
  • BART miRNAs reduced Bim protein levels, but not mRNA levels, suggesting post-transcriptional regulation.
  • The Bim 3' untranslated region (UTR) was implicated in miRNA-mediated repression.

Conclusions:

  • BART miRNAs play a significant role in inhibiting apoptosis in EBV-infected epithelial cancers.
  • BART miRNAs downregulate Bim protein expression post-transcriptionally, partly via the 3'UTR.
  • Additional regulatory sites within the Bim mRNA may exist for BART miRNA recognition.

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