Epstein-Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5

被引:286
作者
Barth, Stephanie [1 ]
Pfuhl, Thorsten [1 ]
Mamiani, Alfredo [1 ]
Ehses, Claudia [1 ]
Roemer, Klaus [2 ]
Kremmer, Elisabeth [3 ]
Jaeker, Christoph [4 ]
Hoeck, Julia [4 ]
Meister, Gunter [4 ]
Graesser, Friedrich A. [1 ]
机构
[1] Univ Saarland, Sch Med, Inst Virol, D-66424 Homburg, Germany
[2] Univ Saarland, Sch Med, Jose Carreras Ctr, Oncol Lab, D-66424 Homburg, Germany
[3] Natl Res Inst Environm & Hlth, GSF, Inst Mol Immunol, D-81377 Munich, Germany
[4] Max Planck Inst Biochem, Lab RNA Biol, D-82152 Martinsried, Germany
关键词
D O I
10.1093/nar/gkm1080
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
MicroRNAs (miRNAs) have been implicated in sequence-specific cleavage, translational repression or deadenylation of specific target mRNAs resulting in post-transcriptional gene silencing. Epstein-Barr virus (EBV) encodes 23 miRNAs of unknown function. Here we show that the EBV-encoded miRNA miR-BART2 down-regulates the viral DNA polymerase BALF5. MiR-BART2 guides cleavage within the 3'-untranslated region (3'UTR) of BALF5 by virtue of its complete complementarity to its target. Induction of the lytic viral replication cycle results in a reduction of the level of miR-BART2 with a strong concomitant decrease of cleavage of the BALF5 3'UTR. Expression of miR-BART2 down-regulates the activity of a luciferase reporter gene containing the BALF5 3'UTR. Forced expression of miR-BART2 during lytic replication resulted in a 40-50% reduction of the level of BALF5 protein and a 20% reduction of the amount of virus released from EBV-infected cells. Our results are compatible with the notion that EBV-miR-BART2 inhibits transition from latent to lytic viral replication.
引用
收藏
页码:666 / 675
页数:10
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