Department of Virology II, National Institute of Infectious Diseases, Tokyo, 162-8640, Japan.
Department of Virology II, National Institute of Infectious Diseases, Tokyo, 162-8640, Japan.
Biochem Biophys Res Commun. 2018 Sep 10;503(3):1854-1860. doi: 10.1016/j.bbrc.2018.07.126. Epub 2018 Jul 25.
Hepatitis B virus (HBV) -x protein is a transcriptional regulator required for the HBV life cycle. HBx also induces complications in the host such as hepatocellular carcinoma. We previously showed that HBx mRNA is degraded by the Ski2/RNA exosome complex. In the present study, we report the regulation of this system through the control of Ski2 expression. We identified interleukin (IL) -1β as an inducer of expression from the Ski2 promoter. IL-1β induced the expression of ATF3 transcription factor, which in turn binds to cyclic AMP-responsive element sequence in the Ski2 promoter and is responsible for Ski2 promoter induction by IL-1β. We previously reported that Ski2 expression increases HBx mRNA degradation; consistent with those data, we showed here that HBx mRNA is degraded in response to IL-1β treatment. Interestingly, HBx also significantly induced Ski2 expression. To our knowledge, this is the first report to show activation of the Ski2/RNA exosome complex by both the host and HBV. Understanding the regulation of the Ski2/RNA exosome system is expected to facilitate prevention of HBx-mediated complications through targeting the posttranscriptional degradation of HBx mRNA; and will also help shedding a light on the role of RNA decay systems in inflammation.
乙型肝炎病毒 (HBV) -x 蛋白是 HBV 生命周期所必需的转录调节剂。HBx 还会导致宿主发生肝癌等并发症。我们之前的研究表明，HBx mRNA 被 Ski2/RNA 外切体复合物降解。在本研究中，我们通过控制 Ski2 表达来调节该系统。我们发现白细胞介素 (IL) -1β 是 Ski2 启动子表达的诱导剂。IL-1β 诱导 ATF3 转录因子的表达，后者反过来与 Ski2 启动子中的环磷酸腺苷反应元件序列结合，负责 IL-1β 诱导 Ski2 启动子。我们之前的报告表明 Ski2 表达增加 HBx mRNA 的降解；与这些数据一致，我们在这里表明 HBx mRNA 在 IL-1β 处理后会被降解。有趣的是，HBx 也显著诱导了 Ski2 的表达。据我们所知，这是首次报道宿主和 HBV 均可激活 Ski2/RNA 外切体复合物。了解 Ski2/RNA 外切体系统的调控有望通过靶向 HBx mRNA 的转录后降解来预防 HBx 介导的并发症；并有助于阐明 RNA 降解系统在炎症中的作用。
