title: Taura syndrome virus IRES initiates translation by binding its tRNA-mRNA-like structural element in the ribosomal decoding center.
abstract: In cap-dependent translation initiation, the open reading frame (ORF) of mRNA is established by the placement of the AUG start codon and initiator tRNA in the ribosomal peptidyl (P) site. Internal ribosome entry sites (IRESs) promote translation of mRNAs in a cap-independent manner. We report two structures of the ribosome-bound Taura syndrome virus (TSV) IRES belonging to the family of Dicistroviridae intergenic IRESs. Intersubunit rotational states differ in these structures, suggesting that ribosome dynamics play a role in IRES translocation. Pseudoknot I of the IRES occupies the ribosomal decoding center at the aminoacyl (A) site in a manner resembling that of the tRNA anticodon-mRNA codon. The structures reveal that the TSV IRES initiates translation by a previously unseen mechanism, which is conceptually distinct from initiator tRNA-dependent mechanisms. Specifically, the ORF of the IRES-driven mRNA is established by the placement of the preceding tRNA-mRNA-like structure in the A site, whereas the 40S P site remains unoccupied during this initial step.
authors.affiliation: RNA Therapeutics Institute, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Cha San
authors.initials: CS
authors.lastname: Koh
authors.affiliation: Department of Biochemistry, Brandeis University, Waltham, MA 02454; and.
authors.forename: Axel F
authors.initials: AF
authors.lastname: Brilot
authors.affiliation: Department of Biochemistry, Brandeis University, Waltham, MA 02454; andHoward Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147 andrei.korostelev@umassmed.edu niko@grigorieff.org.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Grigorieff
authors.affiliation: RNA Therapeutics Institute, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605; andrei.korostelev@umassmed.edu niko@grigorieff.org.
authors.forename: Andrei A
authors.initials: AA
authors.lastname: Korostelev
mesh_terms: D009690:Nucleic Acid Conformation; D016366:Open Reading Frames; D010442:Peptide Chain Initiation, Translational; D010849:Picornaviridae / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral; D012343:RNA, Transfer
keywords: FREALIGN; IRES-dependent initiation; factor-independent initiation; real-space refinement; tRNA-mRNA mimicry