High-resolution structure reveals versatility of RNA nanotechnology

Compared to the more extensively studied DNA nanotechnology route to building complex molecular objects, RNA nanotechnology offers potential advantages because it is capable of a wider variety of small structural motifs. A vivid demonstration of the great structural versatility that can be exploited in building artificial structures of RNA is provided by the first high-resolution structure determination of an artificial RNA nanostructure: a square 6 nm on a side composed of 100 RNA residues that self-assembles from four copies each of two RNA molecules of 10 and 15 residues in length. The structure of this RNA nano-object was determined to a resolution of 0.22 nm and shows that all four corners have distinct structures. Thanks to KurzweilAI-net for pointing to this at the UC San Diego News Center “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.

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.

The abstract of the published research paper (the full text will be available six months after the print publication date):

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 Å 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.

Note: 1 Å = 0.1 nm. We can hope that more high-resolution structures of engineered RNA molecules will follow, and will facilitate more sophisticated RNA molecular engineering.

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