Adenovirus infection controls processing bodies to stabilize AU-rich element-containing mRNA

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.

Automated summary

In adenovirus-infected cells, virus mRNAs are selectively transported into the cytoplasm by virus early gene products, facilitating virus replication. Ribonucleoprotein (RNP) granules in the cytoplasm, involved in mRNA degradation, were analyzed to understand the mechanism of ARE-mRNA stabilization in adenovirus-infected cells. It was found that processing bodies (PBs) aggregate and are then translocated to aggresomes formed by adenoviral gene products. E4orf3 was required for PBs translocation, and the same domains of E4orf3-mutants needed for changing the form of promyelocytic leukemia bodies were also necessary for PBs translocation. Luciferase activity assays showed that these domains were critical for miRNA- and ARE-mediated mRNA decay. These findings suggest that adenovirus alters the behavior of PBs to prevent downregulation of ARE-mRNA.