Cellular UAP56 interacts with the HBx protein of the hepatitis B virus and is involved in viral RNA nuclear export in hepatocytes.

UAP56 is an essential factor in eukaryotic pre-mRNA splicing and mRNA export. Many viruses require cellular RNA export factors to efficiently export viral RNA. However, the mechanisms behind hepatitis B virus (HBV) RNA splicing and nuclear export remain poorly understood. Here, our data show that UAP56 interacts with the HBx protein. Moreover, we demonstrate that the Q-motif of UAP56, which regulates RNA-binding and helicase activity, is essential for the interaction of UAP56 with HBx. Both knockdown of UAP56 and deficiency of HBx impaired cytoplasmic accumulation of HBV RNA transcripts, whereas knockdown of UAP56 also reduced the level of HBV pregenomic RNA splicing variants. In addition, knockdown of Nxf1 induced HBV RNA nuclear accumulation. These findings provide unique insights into the mechanistic details of HBV RNA export and splicing.