Structure of the ribosome-bound cricket paralysis virus IRES RNA.
Internal ribosome entry sites (IRESs) facilitate an alternative, end-independent pathway of translation initiation. A particular family of dicistroviral IRESs can assemble elongation-competent 80S ribosomal complexes in the absence of canonical initiation factors and initiator transfer RNA. We present here a cryo-EM reconstruction of a dicistroviral IRES bound to the 80S ribosome. The resolution of the cryo-EM reconstruction, in the subnanometer range, allowed the molecular structure of the complete IRES in its active, ribosome-bound state to be solved. The structure, harboring three pseudoknot-containing domains, each with a specific functional role, shows how defined elements of the IRES emerge from a compactly folded core and interact with the key ribosomal components that form the A, P and E sites, where tRNAs normally bind. Our results exemplify the molecular strategy for recruitment of an IRES and reveal the dynamic features necessary for internal initiation.
Schüler
Martin
M
Institut für Medizinische Physik und Biophysik, Charite-Universitätsmedizin Berlin, Ziegelstrasse 5-9, 10117-Berlin, Germany.
Connell
Sean R
SR
Lescoute
Aurelie
A
Giesebrecht
Jan
J
Dabrowski
Marylena
M
Schroeer
Birgit
B
Mielke
Thorsten
T
Penczek
Pawel A
PA
Westhof
Eric
E
Spahn
Christian M T
CM
D000818:Animals; D001483:Base Sequence; D020285:Cryoelectron Microscopy; D006135:Gryllidae / Q000821:virology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010243:Paralysis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012328:RNA Viruses / Q000235:genetics*; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D012269:Ribosomal Proteins / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D040681:Structural Homology, Protein
D012367:RNA, Viral; D012269:Ribosomal Proteins; C039913:ribosomal protein S80