RNA: Knots or Not?

No one had checked before, but RNA, the nucleic acid involved in many cell functions including protein synthesis, appears to be the only "strand of life" not to have knots. Over the years, advances in structural biology have firmly established that both proteins and DNA, although subject to evolutionary selection, do not escape the statistical law whereby a sufficiently long and compacted molecular strand will inevitably be entangled. However, no one to date had looked into the case of RNA. Using the structural description provided for approximately 6,000 RNA chains entered in the Protein Data Bank, a public database that allows scientists to share information about the structure of proteins, DNA and RNA, Dr. Cristian Micheletti and Dr. Marco Di Stefano from SISSA, and Dr. Henri Orland from CEA in Saclay set out on a search for knots. "We expected this long, flexible molecule to behave like the others - DNA and proteins - forming knots with a certain frequency", explains Dr. Micheletti. "Instead we were in for a surprise: out of 6,000 known structures only three cases showed 'suspected' knots." Suspected, because the three cases could in fact be artefacts. "The database contains multiple descriptions of the same molecule entered by separate research groups using different experimental techniques with varying resolution. Comparing the alternative descriptions of our 'knotted RNA' candidates, we found no instances of knots. That the three cases may be artefacts is further confirmed by the fact that in all three instances the alternative, unknotted, descriptions were based on the most accurate technique, i.e., x-ray crystallography." These surprising results were published online on February 2, 2015 in PNAS.
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