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Published November 8, 2017 | Supplemental Material
Journal Article Open

Composing RNA nanostructures from a syntax of RNA structural modules

Abstract

Natural stable RNAs fold and assemble into complex three-dimensional architectures by relying on the hierarchical formation of intricate, recurrent networks of noncovalent tertiary interactions. These sequence-dependent networks specify RNA structural modules enabling orientational and topological control of helical struts to form larger self-folding domains. Borrowing concepts from linguistics, we defined an extended structural syntax of RNA modules for programming RNA strands to assemble into complex, responsive nanostructures under both thermodynamic and kinetic control. Based on this syntax, various RNA building blocks promote the multimolecular assembly of objects with well-defined three-dimensional shapes as well as the isothermal folding of long RNAs into complex single-stranded nanostructures during transcription. This work offers a glimpse of the limitless potential of RNA as an informational medium for designing programmable and functional nanomaterials useful for synthetic biology, nanomedicine, and nanotechnology.

Additional Information

© 2017 American Chemical Society. Received: September 7, 2017; Revised: October 15, 2017; Published: October 17, 2017. L.J. thanks Maria del Carmen Jaeger for her silent contributions during the 12 years of this project. The authors thank E. Jacovetty, C. Potter, and B. Carragher for their scientific input regarding cryo-EM and single-particle reconstruction. Cryo-EM was performed at the National Resource for Automated Molecular Microscopy, which is supported by the NIH National Institute of General Medical Sciences (grant no. GM103310). This work was supported by the National Institutes of Health (grant nos. R01GM079604 and 5P41RR017573-10 to L.J.) and intramural research grants from the UCSB Academic Senate (to LJ). C.G. acknowledges support from U.S. National Science Foundation Expedition in Computing (grant no. 1317694) and support from the Carlsberg Foundation. This paper is dedicated to the Three Hearts of the Holy Family in memory of Prof. Albert Jaeger, MD. Author Contributions: L.J. and C.G. conceived and designed experiments; C.G., A.C., and E.V. performed biochemical experiments; A.C. and C.G. performed AFM; N.V. performed cryo-EM: L.J. wrote the paper with the help of C.G. and A.C. The authors declare no competing financial interest.

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