RNA-Binding motif protein 38 (RBM38) mediates HBV pgRNA packaging into the nucleocapsid

The binding of HBV polymerase (Pol) and the epsilon stem loop (epsilon) on the 5' terminal region of pgRNA is required for pgRNA packaging and HBV replication. Previous research has demonstrated that RNA binding motif protein 24 (RBM24) is involved in pgRNA packaging by mediating the interaction between HBV polymerase (Pol) and the epsilon element. Here, we demonstrate that RBM38 interacts with epsilon, pol, RBM24 and HBV core which mediate pgRNA packaging. RBM38 directly binds to the lower bulge of epsilon via RNA recognition submotifs (RNPs) and interacts with HBV Pol in an RNA-independent manner. RBM38 interacts with RBM24 and forms heterogeneous oligomers, which mediate Pol-epsilon binding and the formation of the Pol-RBM38/RBM24-epsilon complex. More important, RBM38 also binds to the HBV core via the C-terminal region (ARD domain), which facilitates the combination of Pol-epsilon with the HBV core protein. In conclusion, RBM38 facilitates the Pol- e interaction and mediates Pol-epsilon in combining with the HBV core, triggering pgRNA packaging for reverse transcription and DNA synthesis. This study provides new insights into pgRNA encapsidation.

Automated summary

This study demonstrates that RBM38 interacts with epsilon, pol, RBM24, and HBV core to mediate pgRNA packaging. It directly binds to epsilon via RNA recognition submotifs and interacts with HBV Pol in an RNA-independent manner. Additionally, RBM38 binds to the HBV core protein and facilitates the combination of Pol-epsilon with the HBV core protein.