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Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Sculpting Responsive, Informational Nano-particles with RNA

Recent progresses have shown that DNA and RNA are particularly suited biopolymers for bionanotechnology (1). For instance, natural RNA molecules comprise the working components of biologically important molecular machines. They make use of a large variety of recurrent, modular, and pre-organized structural motifs that mediate stereochemically precise and readily reversible, tertiary intra- and inter-molecular interactions. Analysis of the rapidly growing structural and sequence databases for RNA has revealed novel RNA-RNA interaction motifs and new topological rules for RNA three-dimensional assembly. ?RNA architectonics? refers to the study and application of the structural principles of modular design and hierarchical folding inferred from natural RNAs to create new nano- and meso-scopic self-assembling architectures (1). RNA is readily amenable to inverse folding: supra-molecular structures can be ?sketched? in 3D space by positioning modular motifs that mediate tertiary interactions to create the desired nano-scale architecture and then connecting the motifs using semi-rigid double helical ?struts?. Consequently, the design can be translated into an appropriate sequence designed to fold uniquely to form the desired structure. The positioning of structural elements can be controlled precisely, by adjusting the lengths of helices and their stacking arrangements at multi-helix junctions (2-4).

We have recently characterized the autonomous folding, thermodynamic, and self-assembly properties of several RNA tertiary structure motifs that can constraint the topology and geometry of contiguous RNA helices to specify for 15°, 90°, 110°, and 180° angle bends (5). Each of these RNA motifs is characterized by a specific sequence signature that is defined as the set of conserved and semi-conserved nucleotides necessary to code for the three-dimensional structure of the motif. It is possible to use these motifs as a structural syntax to design an infinite variety of new RNA three-dimensional shapes by encoding their sequence signatures within new RNA sequences. As a proof of principle, we have used a basic syntax of up to ten different RNA tertiary motifs to design multiple RNA building blocks able to predictably fold and assemble into complex supra-molecular nano-particles with irregular and arbitrary nanoscopic shapes of less than 50 nm (5). Some of these nano-particles are responsive to small molecular effectors such as ATP for triggering the desired folding and supra-molecular assembly (5). Moreover, we have also engineered an ensemble of eight different RNA building blocks that can be controlled to assemble into fully addressable three-dimensional polyhedral cages with an inside and outside (6).

This study shows that RNA architectonics can be used as a tool to explore and compare the biophysical properties of various RNA tertiary structure motifs that would be otherwise more difficult to investigate in isolation or within their natural context. It also demonstrates that RNA is an ideal medium for sculpting addressable and responsive self-assembling architectures of any desired shapes in the 20 to 50 nm scale. Moreover, it suggests that RNA supra-molecular assembly can potentially lead to the development of highly sophisticated therapeutic nano-devices for biological and medical applications.

References and Footnotes
  1. Jaeger, L. and Chworos, A. Current Opinion in Structural Biology 16, 531-543 (2006).
  2. Jaeger, L. and Leontis, N.B. Angew Chem Int Ed Engl 39, 2521-2524 (2000).
  3. Chworos, A, Severcan, I., Koyfman, A. Y., Wienkam, P., Oroudjev, E., Hansma, H. G., and Jaeger, L. Science 306, 2068-2072 (2004).
  4. Nasalean, L., Baudrey, S., Leontis, N.B., and Jaeger, L. Nucleic Acids Res 34, 1381-1392 (2006).
  5. Geary, C., Chworos, A., and Jaeger, L. (in preparation).
  6. Severcan, I., Chworos, A., Geary, C., and Jaeger, L. Spatially Addressable Three-dimensional Cages Made of t-RNA. (in preparation) (2006).

Geary, C.
Severcan, I.
Verzemieks, E.
Chworos, A.
Jaeger, L.*

Department of Chemistry & Biochemistry
Biomolecular Science and Engineering Program
Material Research Laboratory
University of California
Santa Barbara, CA 93106-9510 USA

*Email: jaeger@chem.ucsb.edu