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RNA double helix structure identified using synchrotron light

Scientists prove 50-year-old hypothesis of RNA “higher-order” structure

When Francis Crick and James Watson discovered the double helical structure of deoxyribonucleic acid (DNA) in 1953, it began a genetic revolution to map, study, and sequence the building blocks of living organisms.

A rendering of the poly (rA)11 RNA double helical structure

DNA encodes the genetic material passed on from generation to generation. For the information encoded in the DNA to be made into the proteins and enzymes necessary for life, ribonucleic acid (RNA), single-stranded genetic material found in the ribosomes of cells, serve as intermediary. Although usually single-stranded, some RNA sequences were predicted to have the ability to form a double helix, much like DNA.

In 1961, Alexander Rich along with David Davies, Watson, and Crick, hypothesized that the RNA known as poly (rA) could form a parallel-stranded double helix based on the results of fibre diffraction experiments.

Fifty years later, scientists from McGill University successfully crystallized a short RNA sequence, poly (rA)11, and used data collected at the Canadian Light Source (CLS) and the Cornell High Energy Synchrotron to confirm the hypothesis of a poly (rA) double-helix.

The detailed 3D structure of poly (rA)11 was published by the laboratory of Dr. Kalle Gehring, McGill University, in collaboration with George Sheldrick, University of Göttingen, and Christopher WIlds, Concordia University. The paper appeared in the journal Angewandte Chemie International Edition under the title of “Structure of the Parallel Duplex of Poly (A) RNA: Evaluation of a 50 year-Old Prediction.”

“After 50 years of study, the identification of a novel nucleic acid structure is very rare. So when we came across the unusual crystals of poly (rA), we jumped on it,” said Dr. Gehring.

Gehring said identifying the double-helical RNA will have interesting applications for research in biological nanomaterials and supramolecular chemistry. Nucleic acids have astounding properties of self-recognition and their use as a building material opens new possibilities for the fabrication of bionanomachines – nanoscale devices created using synthetic biology.

“Bionanomachines are advantageous because of their extremely small size, low production cost, and the ease of modification,” said Gehring. “Many bionanomachines already affect our everyday lives as enzymes, sensors, biomaterials, and medical therapeutics.”

Dr. Gehring added that proof of the RNA double helix may have diverse downstream benefits for the medical treatments and cures for diseases like HIV and AIDS, or even to help regenerate biological tissues.

“Our discovery of the poly (rA) structure highlights the importance of basic research. We were looking for information about how cells turn mRNA into protein but we ended up answering a long-standing question from supramolecular chemistry.

For the experiments, Gehring and a team of researchers used data obtained at the CLS Canadian Macromolecular Crystallography Facility (CMCF) to successfully solve the structure of poly (rA)11 RNA.

CMCF Beamline Scientist Michel Fodje said the experiments were very successful in identifying the structure of the RNA and may have consequences for how genetic information is stored in cells.

“Although DNA and RNA both carry genetic information, there are quite a few differences between them,” said Dr. Fodje. “mRNA molecules have poly (rA) tails, which are chemically identical to the molecules in the crystal. The poly (rA) structure may be physiologically important, especially under conditions where there is a high local concentration of mRNA. This can happen where cells are stressed and mRNA becomes concentrated in granules within cells.”

With this information, researchers will continue to map the diverse structures of RNA and their roles in the design of novel bionanomachines and in cells during times of stress.

Reference: Safaee, N., Noronha, A. M., Rodionov, D., Kozlov, G., Wilds, C. J., Sheldrick, G. M., & Gehring, K. (2013). Structure of the Parallel Duplex of Poly (A) RNA: Evaluation of a 50 Year‐Old Prediction. Angewandte Chemie International Edition.

About the Canadian Light Source:

The Canadian Light Source is Canada’s national centre for synchrotron research and a global centre of excellence in synchrotron science and its applications. Located on the University of Saskatchewan campus in Saskatoon, the CLS has hosted 1,700 researchers from academic institutions, government, and industry from 10 provinces and territories; delivered over 26,000 experimental shifts; received over 6,600 user visits; and provided a scientific service critical in over 1,000 scientific publications, since beginning operations in 2005.

CLS operations are funded by Canada Foundation for Innovation, Natural Sciences and Engineering Research Council, Western Economic Diversification Canada, National Research Council of Canada, Canadian Institutes of Health Research, the Government of Saskatchewan and the University of Saskatchewan.

Synchrotrons work by accelerating electrons in a tube at nearly the speed of light using powerful magnets and radio frequency waves. By manipulating the electrons, scientists can select different forms of very bright light using a spectrum of X-ray, infrared, and ultraviolet light to conduct experiments.

Synchrotrons are used to probe the structure of matter and analyze a host of physical, chemical, geological and biological processes. Information obtained by scientists can be used to help design new drugs, examine the structure of surfaces in order to develop more effective motor oils, build more powerful computer chips, develop new materials for safer medical implants, and help clean-up mining wastes, to name a few applications.

Dr. Kalle Gehring | EurekAlert!
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