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PMID: 20400952 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structural aspects of messenger RNA reading frame maintenance by the ribosome.

Nature structural & molecular biology ·Vol. 17 ·No. 5 ·2010-05-00 ·Pages 555-60

Jenner LB, Demeshkina N, Yusupova G, Yusupov M

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.

MeSH Terms
Crystallography, X-Ray Escherichia coli/chemistry,metabolism Models, Molecular Nucleic Acid Conformation RNA, Bacterial/chemistry,metabolism RNA, Messenger/chemistry,metabolism RNA, Transfer/chemistry,metabolism Reading Frames Ribosome Subunits/chemistry,metabolism Thermus thermophilus/chemistry,metabolism
Chemicals
RNA, Bacterial RNA, Messenger RNA, Transfer
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Jenner Lasse B
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Département de Biologie et de Génomique Structurales, Illkirch, France.
Demeshkina Natalia
Yusupova Gulnara
Yusupov Marat
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1790
Published
2010-05-00
Epub
2010-00-18
Pages
555-60
Language
English
Region
United States
NLM ID
101186374
Subset
IM
External Links
PubMed source DOI: 10.1038/nsmb.1790 View journal details
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