Structures of two RNA domains essential for hepatitis C virus internal ribosome entry site function

Translation of the hepatitis C virus (HCV) polyprotein is initiated at an i nternal ribosome entry site (IRES) element in the 5' untranslated region of HCV RNA. The HCV IRES element interacts directly with the 40S subunit, and biochemical experiments have implicated RNA elements near the AUG start co don as required for IRES-40S subunit complex formation. The data we present here show that two RNA stem loops, domains IIId and IIIe, are involved in IRES-40S subunit interaction. The structures of the two RNA domains were so lved by NMR spectroscopy and reveal structural features that may explain th eir role in IRES function.