Hepatitis C Virus IRES RNA-Induced Changes in the Conformation of the 40 S Ribosomal Subunit

Abstract

Initiation of protein synthesis in eukaryotes requires recruitment of the 40 S ribosomal subunit to the messenger RNA (mRNA). In most cases, this depends on recognition of a modified nucleotide cap on the 5′ end of the mRNA. However, an alternate pathway uses a structured RNA element in the 5′ untranslated region of the messenger or viral RNA called an internal ribosomal entry site (IRES). Here, we present a cryo-electron microscopy map of the hepatitis C virus (HCV) IRES bound to the 40 S ribosomal subunit at about 20 Å resolution. IRES binding induces a pronounced conformational change in the 40 S subunit and closes the mRNA binding cleft, suggesting a mechanism for IRES-mediated positioning of mRNA in the ribosomal decoding center.