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A polyhedron made of tRNAs

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Abstract

Supramolecular assembly is a powerful strategy used by nature to build nanoscale architectures with predefined sizes and shapes. With synthetic systems, however, numerous challenges remain to be solved before precise control over the synthesis, folding and assembly of rationally designed three-dimensional nano-objects made of RNA can be achieved. Here, using the transfer RNA molecule as a structural building block, we report the design, efficient synthesis and structural characterization of stable, modular three-dimensional particles adopting the polyhedral geometry of a non-uniform square antiprism. The spatial control within the final architecture allows the precise positioning and encapsulation of proteins. This work demonstrates that a remarkable degree of structural control can be achieved with RNA structural motifs for the construction of thermostable three-dimensional nano-architectures that do not rely on helix bundles or tensegrity. RNA three-dimensional particles could potentially be used as carriers or scaffolds in nanomedicine and synthetic biology.

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Figure 1: Structure and design principles of tRNA-based architectures.
Figure 2: tRNA octamer self-assembly and thermal stability.
Figure 3: Structural characterization of tRNA architectures by AFM.
Figure 4: Structural characterization of tRNA architectures using cryo-EM with single image particle reconstruction.
Figure 5: Coupling streptavidin to spatially addressable antiprisms (TO8–9).

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Change history

  • 26 July 2010

    In Fig. 5f of the version of this Article originally published online, the data for chain lengths of 4 and 5 were presented incorrectly. This error has now been corrected for all versions of the Article.

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Acknowledgements

L.J. wishes to dedicate this paper to St. Luke and St. Marguerite Bourgeoys. Research funding to L.J. was provided by the National Institutes of Health (R01 GM079604). Cryo-EM experiments were conducted at the National Resource for Automated Molecular Microscopy, which is supported by the National Institutes of Health though the ‘National Center for Research Resources’ P41 program (RR17573). The authors thank H. Hansma for the generous use of her AFM and laboratory facilities. We also thank C. Potter and B. Carragher for their scientific input regarding cryo-EM and reconstruction.

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Contributions

I.S. and C.G. contributed equally to this work. I.S., C.G. and L.J. conceived and designed experiments. I.S., C.G. and L.J analysed data. C.G. and L.J. designed the RNA particle and three-dimensional model. I.S. performed PAGE experiments. A.C. performed AFM characterization. N.V. and E.J. performed the cryo-EM characterization and reconstruction. L.J., C.G. and I.S. co-wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Luc Jaeger.

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The authors declare no competing financial interests.

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Severcan, I., Geary, C., Chworos, A. et al. A polyhedron made of tRNAs. Nature Chem 2, 772–779 (2010). https://doi.org/10.1038/nchem.733

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