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Structural basis for messenger RNA movement on the ribosome

Nature volume 444, pages 391–394 (2006)Cite this article

Abstract

Translation initiation is a major determinant of the overall expression level of a gene1,2,3. The translation of functionally active protein requires the messenger RNA to be positioned on the ribosome such that the start/initiation codon will be read first and in the correct frame. Little is known about the molecular basis for the interaction of mRNA with the ribosome at different states of translation. Recent crystal structures of the ribosomal subunits4,5,6,7,8, the empty 70S ribosome9 and the 70S ribosome containing functional ligands10,11,12,13 have provided information about the general organization of the ribosome and its functional centres. Here we compare the X-ray structures of eight ribosome complexes modelling the translation initiation, post-initiation and elongation states. In the initiation and post-initiation complexes, the presence of the Shine–Dalgarno (SD) duplex causes strong anchoring of the 5′-end of mRNA onto the platform of the 30S subunit, with numerous interactions between mRNA and the ribosome. Conversely, the 5′ end of the ‘elongator’ mRNA lacking SD interactions is flexible, suggesting a different exit path for mRNA during elongation. After the initiation of translation, but while an SD interaction is still present, mRNA moves in the 3′→5′ direction with simultaneous clockwise rotation and lengthening of the SD duplex, bringing it into contact with ribosomal protein S2.

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Figure 1: Movement of mRNA on the ribosome.
Figure 2: Path of mRNA with a 5′-terminal extension through the ribosome.
Figure 3: mRNA path at the elongation step.

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Acknowledgements

We thank C. Schulze-Briese and the SLS staff for help with X-ray data collection. This work was funded by CNRS and INSERM. Author Contributions G.Y. and L.J. contributed equally to this work. G.Y. performed the biochemical experiments and crystallized the ribosome complexes. L.J. solved the structures. All authors participated in discussing the results and writing the manuscript.

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Author notes

  1. Gulnara Yusupova and Lasse Jenner: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404, Illkirch cedex, France

    Gulnara Yusupova, Lasse Jenner, Bernard Rees, Dino Moras & Marat Yusupov

Authors
  1. Gulnara Yusupova
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  2. Lasse Jenner
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  3. Bernard Rees
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  4. Dino Moras
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  5. Marat Yusupov
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Corresponding author

Correspondence to Marat Yusupov.

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Competing interests

Coordinates and structure factors have been deposited in the Protein Data Bank under accession numbers 2HGR and 2HGU (initiation complex 30S and 50S subunits), 2HGP and 2HGQ (post-initiation complex) and 2HGI and 2HGJ (mRNA-free complex). Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

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This file contains Supplementary Methods, Supplementary Results, Supplementary Figures and Supplementary Tables. (DOC 563 kb)

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Yusupova, G., Jenner, L., Rees, B. et al. Structural basis for messenger RNA movement on the ribosome. Nature 444, 391–394 (2006). https://doi.org/10.1038/nature05281

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