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Synergistic self-assembly of RNA and DNA molecules

Abstract

DNA has recently been used as a programmable 'smart' building block for the assembly of a wide range of nanostructures. It remains difficult, however, to construct DNA assemblies that are also functional. Incorporating RNA is a promising strategy to circumvent this issue as RNA is structurally related to DNA but exhibits rich chemical, structural and functional diversities. However, only a few examples of rationally designed RNA structures have been reported. Herein, we describe a simple, general strategy for the de novo design of nanostructures in which the self-assembly of RNA strands is programmed by DNA strands. To demonstrate the versatility of this approach, we have designed and constructed three different RNA–DNA hybrid branched nanomotifs (tiles), which readily assemble into one-dimensional nanofibres, extended two-dimensional arrays and a discrete three-dimensional object. The current strategy could enable the integration of the precise programmability of DNA with the rich functionality of RNA.

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Figure 1: DNA-programmed RNA self-assembly: an RNA–DNA hybrid double crossover (DX) motif (tile).
Figure 2: DNA-programmed RNA self-assembly: an RNA–DNA hybrid four-point star motif.
Figure 3: DNA-programmed RNA two-dimensional self-assembly: an RNA–DNA hybrid three-point skewed star motif.
Figure 4: DNA-programmed RNA self-assembly in three dimensions: an RNA–DNA hybrid dodecahedron.

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Acknowledgements

This work was supported by the Office of Naval Research, the National Institutes of Health and a Lilly Seed grant through Purdue University. AFM and DLS studies were carried out in the Purdue Laboratory for Chemical Nanotechnology (PLCN). The cryoEM images were taken in the Purdue Biological Electron Microscopy Facility and the Purdue Rosen Center for Advanced Computing (RCAC) provided the computational resource for the three-dimensional reconstructions.

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S.H.K. and C.Z. prepared samples and gel analysis. S.H.K. and A.E.R. performed AFM and DLS analysis. M.S., C.Z. and W.J. performed cryoEM imaging and three-dimensional reconstruction. All authors analysed the data and wrote the manuscript. C.M. directed the study.

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Correspondence to Chengde Mao.

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The authors declare no competing financial interests.

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Ko, S., Su, M., Zhang, C. et al. Synergistic self-assembly of RNA and DNA molecules. Nature Chem 2, 1050–1055 (2010). https://doi.org/10.1038/nchem.890

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