Self-assembling RNA tertiary architectures

The modularity and singular complementary nature of RNA allows us to control the arrangement of recurring structural motifs that form a wide range of non-covalent tertiary interactions to create hierarchical three-dimensional architectures.  Sequence and structural analysis of identified X-ray RNA motifs has allowed for the development of syntax rules that apply to an RNA proto-language for the design and prediction of RNA 3D shapes.  RNA architectonics involves decoding this proto-language with the goal of constructing novel RNA geometries that can self-assemble.  Through this methodology the tertiary structures of RNA molecules can be predicted and logically designed for possible usage in nanotechnology, synthetic biology and medicine.  In particular, the right angle motif is a common naturally occurring structure that could be incorporated in the construction of RNA nano-cubes, which could be used as scaffolding for quantified si-RNA therapeutics or drug delivery.   To build a stable nano-cube, the structure of the right angle motif must be understood.  For instance, certain sequence regions at the crux of the right angle molecule yield a more rigid structural assembly.  We have experimented with varying right angle sequence designs and have tested the stability of their tertiary structures through binding strength with a probe molecule.  Gel-electrophoresis will be used to demonstrate the binding affinity of the probe molecules to the assembled right angle motifs.  Comparison of our right angle sequence designs to those of naturally occurring right angle structures will help determine which sequences are promising for further RNA nano-construction.