Poly(C)-binding protein interacts with the hepatitis C virus 5' untranslated region

This study demonstrates that poly(C)-binding proteins (PCBPs) 1 and 2 interact with the hepatitis C virus 5' untranslated region (5' UTR). Using biochemical assays, the researchers showed that recombinant GST-PCBP-1 and GST-PCBP-2 fusion proteins bind specifically to the HCV 5' UTR RNA, with binding comparable to other known interacting proteins like PTB. Importantly, the complete internal ribosome entry site (IRES) sequence was required for efficient binding, suggesting that the secondary or tertiary RNA structure is critical for PCBP recognition. The interaction also occurs in human cell cytoplasmic extracts, as demonstrated by supershift experiments using anti-PCBP-2 antibodies. These findings suggest that PCBPs may play functional roles in HCV translation initiation, similar to their characterized roles in poliovirus IRES-dependent translation, though the exact mechanism—whether stimulatory or inhibitory—requires further investigation.

Key findings

• PCBP-1 and PCBP-2 bind specifically to the HCV 5' UTR with comparable affinity to other known binding proteins like PTB
• The complete HCV IRES is necessary for efficient PCBP binding, indicating that RNA secondary structure is essential for protein recognition
• PCBP-IRES interactions occur in living cells, confirmed by supershift assays using anti-PCBP-2 serum in HeLa cell extracts
• PCBPs may have functional roles in HCV translation initiation similar to their roles in poliovirus translation