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

Abstract In Epstein–Barr Virus infected epithelial cancers, the alternatively spliced BamHI A rightward transcripts (BARTs) are abundantly expressed and are the template for two large clusters of miRNAs. This study indicates that both of these clusters independently can inhibit apoptosis in response...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2011-04, Vol.412 (2), p.392-400
Main Authors: Marquitz, Aron R, Mathur, Anuja, Nam, Cyd Stacy, Raab-Traub, Nancy
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Alternative splicing
Antineoplastic Agents, Phytogenic - metabolism
Apoptosis
Apoptosis Regulatory Proteins - antagonists & inhibitors
Apoptosis Regulatory Proteins - genetics
BART
Bcl-2 protein
Bcl-2-Like Protein 11
Bim
BIM protein
Binding Sites
Bioinformatics
Cancer
Cell Line
DNA microarrays
EBV
Epithelial cells
Epithelial Cells - drug effects
Epithelial Cells - virology
Epstein-Barr virus
Etoposide
Etoposide - metabolism
Gene expression
Herpesvirus 4, Human - immunology
Herpesvirus 4, Human - pathogenicity
Humans
Immune Evasion
Infectious Disease
Membrane Proteins - antagonists & inhibitors
Membrane Proteins - genetics
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Post-transcription
Proto-Oncogene Proteins - antagonists & inhibitors
Proto-Oncogene Proteins - genetics
RNA, Messenger - genetics
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Summary:Abstract In Epstein–Barr Virus infected epithelial cancers, the alternatively spliced BamHI A rightward transcripts (BARTs) are abundantly expressed and are the template for two large clusters of miRNAs. This study indicates that both of these clusters independently can inhibit apoptosis in response to etoposide in an epithelial cell line. The Bcl-2 interacting mediator of cell death (Bim) was identified using gene expression microarrays and bioinformatic analysis indicated multiple potential binding sites for several BART miRNAs in the Bim 3′UTR. Bim protein was reduced by Cluster I and the individual expression of several miRNAs, while mRNA levels were unaffected. In reporter assays, the Bim 3′ untranslated region (UTR) was inhibited by both clusters but not by any individual miRNAs. These results are consistent with the BART miRNAs downregulating Bim post-transcriptionally in part through the 3′UTR and suggest that there are miRNA recognition sites within other areas of the Bim mRNA.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2011.01.028