Adenovirus infection controls processing bodies to stabilize AU-rich element-containing mRNA
Adenovirus infection controls processing bodies to stabilize AU-rich element-containing mRNA
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DOI：
10.1016/j.virol.2022.06.009
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发表时间：
2022-06-30
期刊：
影响因子：
3.7
通讯作者：
Higashino，Fumihiro
中科院分区：
文献类型：
--
作者：
Kuroshima，Takeshi;Matsuda，Aya Yanagawa;Higashino，Fumihiro
在腺病毒感染的细胞中，病毒mRNA通过病毒早期基因产物选择性输出至细胞质，以促进病毒复制。我们之前表明，含有 mRNA 的富含 AU 元件 (ARE) 被输出到细胞质并在受感染的细胞中稳定下来。在这里，我们分析了细胞质中参与 mRNA 降解的核糖核蛋白 (RNP) 颗粒，以阐明腺病毒感染细胞中 ARE-mRNA 稳定的机制。我们的研究结果表明，加工体（PB）聚集，然后几乎所有的PB在感染后期都被转移到由腺病毒基因产物形成的聚集体中。此外，PBs易位需要E4orf3，并且PBs易位也需要改变早幼粒细胞白血病体形式所需的E4orf3突变体的相同结构域。荧光素酶活性表明这些结构域对于 miRNA 和 ARE 介导的 mRNA 衰减至关重要。这些发现表明腺病毒改变 PB 的行为以防止 ARE-mRNA 下调。
In the adenovirus-infected cells, virus mRNAs are selectively exported to the cytoplasm by virus early gene products to facilitate virus replication. We previously showed AU-rich elements (AREs) containing mRNAs are exported to the cytoplasm and stabilized in infected cells. Here, we analyzed ribonucleoprotein (RNP) granules in the cytoplasm that are involved in mRNA degradation to elucidate the mechanism of ARE-mRNA stabilization in adenovirus infected cells. Our findings showed that processing bodies (PBs) aggregate, then almost all PBs are translocated to aggresomes formed by adenoviral gene products during the late phase of infection. Furthermore, E4orf3 was required for the PBs translocation, and the same domains of E4orf3-mutants required to change the form of promyelocytic leukemia bodies were also needed for PBs translocation. Luciferase activity showed that these domains were critical for miRNA- and ARE-mediated mRNA decay. These findings suggest that adenovirus changes the behavior of PBs to prevent ARE-mRNA downregulation.