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A new method called R2D2 – which stands for "reconstructing RNA dynamics from data" and is completely unrelated to the beepy droid from Star Wars – has generated some amazing videos that allow us to see how RNA folds. “Folding takes place in your body more than 10 quadrillion times a second,” said leader of the study and associate professor of chemical and biological engineering, Julius B. Lucks, in a statement, “It happens every single time a gene is expressed in a cell, yet we know so little about it. Our movies allow us to finally watch folding happen for the first time.”
The study in Molecular Cell focused on the non-coding RNA SRP from E. coli, which is ancient and found in all kingdoms of life. This RNA forms part of the signal recognition particle (SRP) that binds to newly made peptides, targeting them to specific locations in the cell. It has a signature long hairpin shape, with several internal bulges. R2D2 revealed that it contorts itself in a variety of ways before ending up in its final form. The SRP RNA ties itself into a knot before rapidly untying itself and flipping into a hairpin, which sounds like a gold medal-winning gymnastics routine, but is actually a process called toehold mediated strand displacement. “We think the RNA has evolved to untie itself from knots because if knots persist, it can render the RNA nonfunctional. The structure is so essential to life that it had to evolve to find a way to get out of a knot,” explained Lucks.
Previous data on RNA folding was complex and full of approximations, and could not be directly used to obtain the models of specific RNA structures. R2D2 works by sampling possible RNA structures from structural data on the RNA, then using an algorithm to select the structures most consistent with experimental data. “The information that we give the algorithms helps the computer models correct themselves,” said Lucks, “The model makes accurate simulations that are consistent with the data.”
These structures are connected to 3D dynamic modeling, producing these fascinating videos. Several of R2D2’s structural predictions have been backed up by another study that used high-resolution optical tweezers.
These findings could tear down barriers to understanding and treating diseases related to RNA.“RNA is a really important piece of diagnostic and therapeutic design. The more we know about RNA folding and complexities, the better we can design treatments,” stated Lucks.
