title: tRNA-mRNA mimicry drives translation initiation from a viral IRES.
abstract: Internal ribosome entry site (IRES) RNAs initiate protein synthesis in eukaryotic cells by a noncanonical cap-independent mechanism. IRESes are critical for many pathogenic viruses, but efforts to understand their function are complicated by the diversity of IRES sequences as well as by limited high-resolution structural information. The intergenic region (IGR) IRESes of the Dicistroviridae viruses are powerful model systems to begin to understand IRES function. Here we present the crystal structure of a Dicistroviridae IGR IRES domain that interacts with the ribosome's decoding groove. We find that this RNA domain precisely mimics the transfer RNA anticodon-messenger RNA codon interaction, and its modeled orientation on the ribosome helps explain translocation without peptide bond formation. When combined with a previous structure, this work completes the first high-resolution description of an IRES RNA and provides insight into how RNAs can manipulate complex biological machines.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado at Denver and Health Sciences Center, Mail Stop 8101, PO Box 6511, Aurora, Colorado 80045, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Costantino
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Pfingsten
authors.forename: Robert P
authors.initials: RP
authors.lastname: Rambo
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kieft
mesh_terms: D000926:Anticodon / Q000235:genetics; D001665:Binding Sites; D016174:Hepacivirus / Q000235:genetics; D008957:Models, Genetic; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000502:physiology*
chemical_list: D000926:Anticodon; D012333:RNA, Messenger; D012367:RNA, Viral; D012343:RNA, Transfer