Scientists image RNA folding in real time
- EMBL researchers Kavan Gor, Eva Maria Geissen, and Olivier Duss reported a way to watch single nascent RNA molecules fold in real time. - Their multicolor fluorescence setup functionally tracked up to 8 RNA types and showed proteins, enzymes, and antisense oligos reshape only subsets of folding states. - That matters because RNA usually gets measured as static snapshots, while function often depends on brief, hard-to-catch intermediate structures.
RNA is not just a string of letters. It is a moving molecule that starts folding while it is still being made, and those shape changes decide what it can do next. The problem is that most tools give you snapshots after the fact. You see the poses, but not the dance. A new paper from Kavan Gor, Eva Maria Geissen, and Olivier Duss at EMBL gets much closer to the dance itself by tracking nascent RNA folding in real time at the single-molecule level. (science.org) ### What exactly is new here? The team built multicolor single-molecule fluorescence experiments that watch RNA structure form as the RNA emerges from RNA polymerase. That matters because cotranscriptional folding is where many important decisions get locked in. Instead of averaging over huge numbers of molecules, they followed individual molecules and sorted them into distinct folding classes. The paper was published in *Science Advances* on March 20, 2026. (science.org) ### Why is “real time” such a big deal? Because RNA does not fold once and stay put. It samples multiple conformations, including short-lived intermediates that can disappear before conventional assays catch them. Older structural mapping methods have been great at telling scientists what states exist, but much worse at showing how one state turns into another, or which path actually leads to function. This method adds the missing kinetic view. (science.org) ### What were they actually watching? They were watching nascent RNA — RNA that is still being synthesized — and asking how its local accessibility changes over time. In plain English, they used fluorescent readouts to tell when specific regions were exposed or tucked away in base-paired structures. That lets them infer when helices form, when they rearrange, and when different molecules of the same sequence split into different structural fates. (science.org) ### What did they find? One big result is that folding is not one clean pathway. The same RNA can populate multiple classes, and outside factors push only some of those classes around. The team showed that ribosomal proteins, RNA modification enzymes, and antisense oligonucleotides do not simply “fold the RNA correctly” in a uniform way. They selectively reshape parts of the ensemble. That is a more realistic picture of how cells work. (science.org) ### Why do ribosomal proteins matter here? Because the paper gives direct evidence that increased local RNA accessibility at specific sites tracks with the chaperoning activity of ribosomal proteins during ribosome assembly. Basically, some proteins are not just binding finished RNA structures. They are helping steer the folding route while the RNA is still under construction. That is a stronger m(science.org)easurement can usually provide. (science.org) ### What about drug design? This does not instantly produce RNA drugs. But it gives drug hunters a better map of which transient structures are real, which ones matter, and which interventions shift the ensemble. That is especially relevant for antisense oligonucleotides, which work by binding accessible RNA regions. If accessibility flickers on and off during folding, timing and pathway suddenly (science.org) point is an inference from the paper’s results, but it is a pretty direct one. (science.org) ### How does this fit with older RNA methods? Think of the older methods as still photography and this as live video. Snapshot methods remain incredibly useful — they can cover more molecules and often more conditions. But they flatten time. This approach complements them by revealing sequence, timing, and heterogeneity — the stuff you need if misfolding, remodeling, or transient accessibility is the whole story. (science.org) ### Bottom line The advance here is not that scientists finally proved RNA folds. Everyone knew that. The advance is that they can now watch individual RNA molecules choose among competing folding paths while those choices are still happening. For RNA biology — and eventually RNA therapeutics — that is a much more useful thing to know. (science.org)
