Hepatitis B virus polymerase suppresses translation of pregenomic RNA via a mechanism involving its interaction with 5' stem-loop structure.
The pregenomic RNA (pgRNA) of hepadnaviruses serves a dual role: as mRNA for the core (C) and polymerase (P) synthesis and as an RNA template for viral genome replication. A question arises as to how these two roles are regulated. We hypothesized that the P protein could suppress translation of the pgRNA via its interaction with 5' stem-loop structure (epsilon or encapsidation signal). Consistent with the hypothesis, we observed up-regulation of the C protein level in the absence of the P protein expression in a physiological context. Importantly, translational suppression depended on the 5' epsilon sequence. Furthermore, the impact of the P protein on ongoing translation of the C ORF was directly demonstrated by polysome distribution analysis. We conclude that the P protein suppresses translation of the pgRNA via a mechanism involving its interaction with the 5' epsilon sequence, a finding that implicates the coordinated switch from translation to genome replication.
D020121:5' Untranslated Regions / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects*; D012313:RNA / Q000187:drug effects* / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism* / Q000494:pharmacology; D014162:Transfection; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D020121:5' Untranslated Regions; D012367:RNA, Viral; D014758:Viral Core Proteins; C100808:pgRNA; D012313:RNA; D012194:RNA-Directed DNA Polymerase