Methyltransferase PRMT1 Is a Binding Partner of HBx and a Negative Regulator of Hepatitis B Virus Transcription
Methyltransferase PRMT1 Is a Binding Partner of HBx and a Negative Regulator of Hepatitis B Virus Transcription
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DOI：
10.1128/jvi.02574-12
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发表时间：
2013-04-01
影响因子：
5.4
通讯作者：
Neuveut, Christine
中科院分区：
文献类型：
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作者：
Benhenda, Shirine;Ducroux, Aurelie;Neuveut, Christine
B型肝炎病毒X蛋白（HBx）是病毒复制所必需的，并与肝癌的发展有关。HBx被募集到病毒和细胞启动子，并通过与转录因子和共激活因子相互作用来激活转录。在这里，我们从HepG2肝癌细胞的核提取物中纯化HBx相关因子，并确定蛋白质精氨酸甲基转移酶1（PRMT1）作为一种新的HBx相互作用蛋白。我们发现PRMT 1过表达降低了B型肝炎病毒（HBV）的转录，这种抑制依赖于PRMT 1的甲基转移酶功能。相反，PRMT1的缺失与HBV转录增加相关。使用定量染色质免疫沉淀分析，我们发现PRMT1被募集到HBV DNA，表明PRMT1对HBV转录的调节有直接作用。最后，我们发现HBx表达抑制PRMT1介导的蛋白质甲基化。在体内动物模型中，在HBV复制细胞中进一步观察到PRMT1活性下调。总之，我们的研究结果支持HBx与PRMT1的结合可能通过减轻PRMT1对HBV转录的抑制活性而有益于病毒复制的观点。
The hepatitis B virus X protein (HBx) is essential for virus replication and has been implicated in the development of liver cancer. HBx is recruited to viral and cellular promoters and activates transcription by interacting with transcription factors and coactivators. Here, we purified HBx-associated factors in nuclear extracts from HepG2 hepatoma cells and identified protein arginine methyltransferase 1 (PRMT1) as a novel HBx-interacting protein. We showed that PRMT1 overexpression reduced the transcription of hepatitis B virus (HBV), and this inhibition was dependent on the methyltransferase function of PRMT1. Conversely, depletion of PRMT1 correlated with increased HBV transcription. Using a quantitative chromatin immunoprecipitation assay, we found that PRMT1 is recruited to HBV DNA, suggesting a direct effect of PRMT1 on the regulation of HBV transcription. Finally, we showed that HBx expression inhibited PRMT1-mediated protein methylation. Downregulation of PRMT1 activity was further observed in HBV-replicating cells in an in vivo animal model. Altogether, our results support the notion that the binding of HBx to PRMT1 might benefit viral replication by relieving the inhibitory activity of PRMT1 on HBV transcription.