Some viruses tie their RNA into intricate knots to prevent hostile cells from digesting it. Experiments now show that the Zika virus’s knotted RNA is the most stable RNA ever observed, paving the way to understanding how the virus eludes cellular defences.
To study the knot’s mechanics, Meng Zhao and Michael Woodside at the University of Alberta in Canada used optical tweezers, which rely on a laser beam to hold and move microscopic objects. The authors applied force to both of the RNA strand’s free ends, allowing them to repeatedly unfold and refold the knot and observe the steps involved in its formation. This revealed that a ring-shaped structure blocks the cell’s enzymes from digesting the RNA and generates the knot’s unusual mechanical stability.
By working out the steps required to form the ring, the researchers offer potential targets for future therapeutics to prevent the RNA from knotting. Many members of the flavivirus family — which includes the Zika, West Nile, dengue and yellow fever viruses — contain RNA with knots, and the authors hope their findings will contribute to disarming these viruses.