Deciphering RNA 3D Structure Now Possible with Novel Technique

Our world is run by RNA, the vital sibling of the genetic molecule DNA. Evolutionary biologists have long hypothesized that RNA existed and has self-replicated long before the appearance of DNA and the proteins that are encoded by it. Science has now revealed that less than three percent of the human genome is transcribed into mRNA, and messenger RNA, which in turn are translated into the various proteins in the body. Compared to the roughly 82% of the molecule that is transcribed into RNA molecules with a myriad of other functions many of which still remain a mystery today.

Novel Technique Enables the 3D Structural Analysis of RNA Genetic Molecules

To gain a better understanding of what an individual RNA molecule can do, the 3D structure of the molecule must be deciphered and analyzed at the level of its constituent atoms and what molecular bonds it has. Researchers have studied DNA molecules routinely by turning them into regularly packed crystals that allow researchers to examine them with X-ray beams or radio waves.

Unfortunately, the same tried-and-tested techniques cannot be used on RNA molecules because the composition and structural flexibility of the molecules prevents them from forming crystals easily.

This is why a collaboration of researchers led by Peng Yin, Ph.D., Wyss Core Faculty member from Harvard University, and Maofu Liao, Ph.D. from Harvard Medical School reported a fundamentally novel approach to investigating the structure of RNA molecules.

Dubbed ROCK, the novel method uses RNA nanotechnological techniques which allow researchers to assemble various identical RNA molecules and multiply their weight. Applied to well-known RNA models with different sizes and functions as benchmarks, the team was able to demonstrate their method which enabled the structural analysis of the contained RNA subunits in a technique known as cryo-electron microscopy. The breakthrough was reported in a study published in the journal Nature Methods, titled "Sub-3-Å cryo-EM structure of RNA enabled by engineered homomeric self-assembly".

Yin explains that ROCK is a novel technique that breaks through current limitations of RNA structural analysis while enabling 3D structures of the molecule to be unlocked that were once difficult and nearly impossible to access with conventional methods at near-atomic resolutions. Adding that the team hopes that the advancement invigorates numerous areas of fundamental research and drug development, including RNA therapeutics.

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Control Over RNA and its Structure

Yin's team has pioneered numerous approaches that allow DNA and RNA molecules to self-assemble into vast structures based on different principles and requirements, which include DNA bricks and DNA origami. The team hypothesized that such strategies could also be used to assemble naturally occurring RNWA molecules into more ordered circular complexes wearing their freedom to move and flex isn't highly restricted specifically when linking the molecules together, reports NewsMedical.

Various RNAs fold in complicated yet unpredictable ways, small segments of base-pairing with each other can be seen in different kinds of literature. This results in often a stabilized core and stem loops that bulge from the molecule's periphery.