UC San Diego Chemists Produce First High-Resolution RNA “Nano Square”

Chemists at UC San Diego have produced the first high resolution structure of a nano-scale square made from ribonucleic acid, or RNA. The structure was published in a paper in this week’s early online edition of the journal Proceedings of the National Academy of Sciences by a team of chemists headed by Thomas Hermann, an assistant professor of chemistry and biochemistry at UCSD.

Journal Proceedings of the National Academy of Sciences – Self-assembling RNA square

Stereo view of the crystal packing of the self-assembling RNA square. View of next neighbors in adjacent planes of squares. Strands are colored according to B factors (blue = low, red = high B factors).

The three-dimensional structures of noncoding RNA molecules reveal recurring architectural motifs that have been exploited for the design of artificial RNA nanomaterials. Programmed assembly of RNA nanoobjects from autonomously folding tetraloop–receptor complexes as well as junction motifs has been achieved previously through sequence-directed hybridization of complex sets of long oligonucleotides. Due to size and complexity, structural characterization of artificial RNA nanoobjects has been limited to low-resolution microscopy studies. Here we present the design, construction, and crystal structure determination at 2.2 angstroms of the smallest yet square-shaped nanoobject made entirely of double-stranded RNA. The RNA square is comprised of 100 residues and self-assembles from four copies each of two oligonucleotides of 10 and 15 bases length. Despite the high symmetry on the level of secondary structure, the three-dimensional architecture of the square is asymmetric, with all four corners adopting distinct folding patterns. We demonstrate the programmed self-assembly of RNA squares from complex mixtures of corner units and establish a concept to exploit the RNA square as a combinatorial nanoscale platform.

The scientists said the ability to carry structural information encoded in the sequence of the constituent building blocks is a characteristic trait of RNA, a key component of the genetic code. The nano square self-assembles from four corner units directed by the sequence that was programmed into the RNA used for preparing the corners. Hermann said the RNA square has potential applications as a self-assembling nano platform for the programmed combination of molecular entities that are linked to the corner units

Crystal packing of the self-assembling RNA square. View of next neighbors within a plane of squares.

14 pages of supplemental information

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