title: Crystal structure of the HCV IRES central domain reveals strategy for start-codon positioning.
abstract: Translation of hepatitis C viral proteins requires an internal ribosome entry site (IRES) located in the 5' untranslated region of the viral mRNA. The core domain of the hepatitis C virus (HCV) IRES contains a four-way helical junction that is integrated within a predicted pseudoknot. This domain is required for positioning the mRNA start codon correctly on the 40S ribosomal subunit during translation initiation. Here, we present the crystal structure of this RNA, revealing a complex double-pseudoknot fold that establishes the alignment of two helical elements on either side of the four-helix junction. The conformation of this core domain constrains the open reading frame's orientation for positioning on the 40S ribosomal subunit. This structure, representing the last major domain of HCV-like IRESs to be determined at near-atomic resolution, provides the basis for a comprehensive cryoelectron microscopy-guided model of the intact HCV IRES and its interaction with 40S ribosomal subunits.
authors: Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Katherine E
authors: KE
authors: Berry
authors: Shruti
authors: S
authors: Waghray
authors: Stefanie A
authors: SA
authors: Mortimer
authors: Yun
authors: Y
authors: Bai
authors: Jennifer A
authors: JA
authors: Doudna
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D018387:Codon, Initiator / Q000737:chemistry*; D019295:Computational Biology; D020285:Cryoelectron Microscopy; D016174:Hepacivirus / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D012333:RNA, Messenger / Q000737:chemistry*; D012367:RNA, Viral / Q000737:chemistry*; D054682:Ribosome Subunits, Small, Eukaryotic / Q000737:chemistry*; D012270:Ribosomes / Q000737:chemistry; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000737:chemistry
chemical_list: D018387:Codon, Initiator; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins