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

被引：273

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

来源：

NUCLEIC ACIDS RESEARCH | 2008年 / 36卷 / 02期

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 ; 081704 ;

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

页码：666 / 675

页数：10

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