title: Structural aspects of messenger RNA reading frame maintenance by the ribosome.
abstract: One key question in protein biosynthesis is how the ribosome couples mRNA and tRNA movements to prevent disruption of weak codon-anticodon interactions and loss of the translational reading frame during translocation. Here we report the complete path of mRNA on the 70S ribosome at the atomic level (3.1-A resolution), and we show that one of the conformational rearrangements that occurs upon transition from initiation to elongation is a narrowing of the downstream mRNA tunnel. This rearrangement triggers formation of a network of interactions between the mRNA downstream of the A-site codon and the elongating ribosome. Our data elucidate the mechanism by which hypermodified nucleoside 2-methylthio-N6 isopentenyl adenosine at position 37 (ms(2)i(6)A37) in tRNA(Phe)(GAA) stabilizes mRNA-tRNA interactions in all three tRNA binding sites. Another network of contacts is formed between this tRNA modification and ribosomal elements surrounding the mRNA E/P kink, resulting in the anchoring of P-site tRNA. These data allow rationalization of how modification deficiencies of ms(2)i(6)A37 in tRNAs may lead to shifts of the translational reading frame.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Département de Biologie et de Génomique Structurales, Illkirch, France.
authors.forename: Lasse B
authors.initials: LB
authors.lastname: Jenner
authors.forename: Natalia
authors.initials: N
authors.lastname: Demeshkina
authors.forename: Gulnara
authors.initials: G
authors.lastname: Yusupova
authors.forename: Marat
authors.initials: M
authors.lastname: Yusupov
mesh_terms: D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D012329:RNA, Bacterial / Q000737:chemistry* / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism; D016364:Reading Frames; D054657:Ribosome Subunits / Q000737:chemistry* / Q000378:metabolism; D016963:Thermus thermophilus / Q000737:chemistry* / Q000378:metabolism
chemical_list: D012329:RNA, Bacterial; D012333:RNA, Messenger; D012343:RNA, Transfer
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