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

The Epstein-Barr Virus BART microRNAs target the pro-apoptotic protein Bim.
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DOI:
10.1016/j.virol.2011.01.028
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发表时间:
2011-04-10
期刊:
影响因子:
3.7
通讯作者:
Raab-Traub N
Raab-Traub N
中科院分区:
医学3区
文献类型:
--
作者:
Marquitz AR;Mathur A;Nam CS;Raab-Traub N

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在Epstein-Barr病毒感染的上皮癌中,可选剪接的BamHI A向右转录物(BARTs)大量表达,并且是两个大mirna簇的模板。本研究表明,这两种簇均可独立抑制上皮细胞系对依托泊苷的凋亡反应。利用基因表达微阵列鉴定了细胞死亡(Bim)的Bcl-2相互作用介质,生物信息学分析表明,Bim 3'UTR Bim蛋白中多个BART mirna的潜在结合位点被簇I和几个mirna的个体表达减少,而mRNA水平未受影响。在报告者分析中,Bim 3'非翻译区(UTR)被这两个簇抑制,但不被任何单个mirna抑制。这些结果与BART miRNA在转录后部分通过3'UTR下调Bim一致,并表明在Bim mRNA的其他区域存在miRNA识别位点。
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.
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