A key role for the exoribonuclease XRN1 in regulating the hepatitis B viral transcriptome.

Chronic hepatitis B virus (HBV) is a leading cause of liver disease and hepatocellular carcinoma that persists as a DNA mini-chromosome and replicates via genomic RNA intermediates. While HBV replication has been extensively studied, mechanisms governing viral RNA degradation remain unclear. Here, we identify a key role for the 5′-3′ exoribonuclease XRN1 in regulating the HBV transcriptome. Pharmacologic inhibition or genetic ablation of XRN1 increased HBV subgenomic RNAs without affecting pregenomic RNA (pgRNA) levels. Long-read RNA-seq showed that subgenomic RNAs, but not pgRNA, are degraded by XRN1, consistent with differential 5′ cap modification and processing (P-) body localisation. HBV infection increased P-body number and size, and delivery of synthetic pgRNA demonstrated that active replication, not RNA expression alone, alters the abundance of P-bodies. These findings identify XRN1 as a key regulator of HBV RNA turnover and uncover a mechanism for viral replication to remodel host RNA dynamics.
This archive contains the original uncropped images and western blots used in the manuscript, together with the numerical values used in the graphs.