Scientists fold RNA origami from a single strand

Aug 14, 2014
This is a computer graphic of an RNA molecule. Credit: Richard Feldmann/Wikipedia

RNA origami is a new method for organizing molecules on the nanoscale. Using just a single strand of RNA, many complicated shapes can be fabricated by this technique. Unlike existing methods for folding DNA molecules, RNA origamis are produced by enzymes and they simultaneously fold into pre-designed shapes. These features may allow designer RNA structures to be grown within living cells and used to organize cellular enzymes into biochemical factories. The method, which was developed by researchers from Aarhus University (Denmark) and California Institute of Technology, is reported in the latest issue of Science.

Origami, the Japanese art of paper folding, derives its elegance and beauty from the manipulation of a single piece of paper to make a complex shape. The RNA method described in the new study likewise involves the folding of a single strand of RNA, but instead of the experimenters doing the folding, the molecules fold up on their own.

"What is unique about the method is that the folding recipe is encoded into the molecule itself, through its sequence." explains Cody Geary, a postdoctoral scholar in the field of RNA structure and design at Aarhus University. "The sequence of the RNAs defines both the final shape and also the series of movements that rearrange the structures as they fold."

"The challenge of designing RNAs that fold up on their own is particularly difficult, since the molecules can easily get tangled during the folding process. So to design them, you really have to imagine the way that the molecules must twist and bend to obtain their final shape." Geary says.

The researchers used 3D models and computer software to design each RNA origami, which was then encoded as a synthetic DNA gene. Once the DNA gene was produced, simply adding the enzyme RNA-polymerase resulted in the automatic formation of RNA origami.

To observe the RNA molecules the researchers used an atomic force microscope, a type of scanning microscope that softly touches molecules instead of looking at them directly. The microscope is able to zoom in a thousand times smaller than is possible with a conventional light microscope. The researchers have demonstrated their method by folding RNA structures that form honeycomb shapes, but many other shapes should be realizable.

"We designed the RNA molecules to fold into honeycomb patterns because they are easy to recognize in the microscope. In one experiment we caught the polymerases in the process of making the RNAs that assemble into honeycombs, and they really look like honey bees in action." Geary continues.

A method for making origami shapes out of DNA has been around for almost a decade, and has since created many applications for molecular scaffolds. However, RNA has some important advantages over its chemical cousin DNA that make it an attractive alternative:

Paul Rothemund, a research professor at the California Institute of Technology and the inventor of the DNA origami method, is also an author on the new RNA origami work. "The parts for a DNA origami cannot easily be written into the genome of an organism. RNA origami, on the other hand, can be represented as a DNA gene, which in cells is transcribed into RNA by a protein machine called RNA polymerase." explains Rothemund.

Rothemund further adds, "The payoff is that unlike DNA origami, which are expensive and have to be made outside of cells, RNA origami should be able to be grown cheaply in large quantities, simply by growing bacteria with genes for them. Genes and bacteria cost essentially nothing to share, and so RNA origami will be easily exchanged between scientists."

The research was performed at laboratories at Aarhus University in Denmark, and the California Institute of Technology in Pasadena. Ebbe Andersen, an Assistant Professor at Aarhus University, who works on developing molecular biosensors, lead the development of the project.

"All of the and structures that form inside of living cells are the products of self-assembly, but we still know very little about how self-assembly actually works. By designing and testing self-assembling RNA shapes, we have begun to shed some light on fundamental principles of self-assembly." says Andersen.

"The primary application for these molecular shapes is to build scaffolds for arranging other microscopic components, such as proteins, into groups that allow them to work together. For example, using the scaffolds as a foundation to build a microscopic chemical factory in which products are passed from one protein enzyme to the next." Andersen explains.

Explore further: Choreographed origami: Folding ribosomal RNA requires paired tagging sequence

More information: A single-stranded architecture for cotranscriptional folding of RNA nanostructures, Science 15 August 2014: Vol. 345 no. 6198 pp. 799-804. DOI: 10.1126/science.1253920

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not rated yet Aug 14, 2014
Synthetic biology could solve medical and energy problems that nanotechnologists hoped/thought nano-manufacturing would solve. But, nanomanufacturing is still desired for manufacturing of materials on both a nanoscale and macroscale. Synthetic biology cannot do this; the question in my mind was always, how can we combine synthetic biology with dna-nanotechnology?

Well, maybe dna-nanotechnology still isn't quite combined with synthetic biologoy; but, here, we have rna-nanotechnology combined with synthetic biology!
1 / 5 (1) Aug 14, 2014
The fundamental principles of self-assembly are biophysically constrained in the context of thermodynamic cycles of protein biosynthesis and degradation that must lead to organism-level thermoregulation in organisms that can acquire nutrients and metabolize them to species-specific pheromones that control cell type differentiation via the conserved molecular mechanisms of alternative splicings of pre-mRNA and amino acid substitutions.

Evolutionary theorists who have suggested that mutations might somehow be beneficial in the context of the fundamental principles of self-assembly should now attempt to explain themselves in the context of RNA origami (i.e., self-assembling RNA shapes).

Serious scientists should show the evolutionary theorists what happens when a mutation causes a change in protein-folding. Evolutionary theory could then be trashed along with the wasted paper used to demonstrate biologically-based cause and effect to the theorists.
1 / 5 (1) Aug 14, 2014
The evolutionary origin of form and function http://onlinelibr...775/full

Excerpt: The evolution of multicellular organisms with complex forms and functional abilities can be accounted for based on a fundamental tenet underpinned by the second law of thermodynamics, with natural selection acting on the ability of the organism to transduct energy (nutrient) most efficiently from its ecosystem by deploying that form and those functions. The information that gives rise to form and function is dispersed throughout the organism in the constituent cellular phenotypes and derives mainly from the interactions between information bearing proteins. The concept of a gene, beyond a means of specifying the amino acid sequences of the peptides from which the proteins are formed, is both mostly unnecessary and possibly misleading.
5 / 5 (1) Aug 15, 2014

From http://www.scienc...1100010X

"In humans, the vomeronasal (pheromone receptor) organ develops in utero but subsequently regresses; all studies agree on its nonfunctional status."

Modern genomics don't lie.

JVK - James V Kohl, you are a spammer and a scammer.

I will keep calling it out and if you continue here I am going to start doing it on the various other forums you post your snake oil crap on like pherotalk et. al. Don't forget pubmed has comments too.

1 / 5 (1) Aug 15, 2014

"From the microbe's perspective, what we eat is a matter of life and death," Dr. Maley said.

The life and death of all organisms is nutrient-dependent and pheromone-controlled and conserved molecular mechanisms link ecological variation to ecological adaptations in their morphology and behavior.

The idea that someone could discredit the only accurate perspective on the direct link from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man, is as ridiculous as the theory that mutation-initiated natural selection led to the evolution of any species that needs food to survive.

The de novo creation of olfactory receptor genes links species from microbes to man, not mutation-driven evolution.

Nutrient-dependent/pheromone-controlled adaptive evolution: a model