Compaction of RNA Duplexes in the Cell

The structure and flexibility of RNA depends sensitively on the microenvironment. Using pulsed electron‐electron double‐resonance (PELDOR)/double electron‐electron resonance (DEER) spectroscopy combined with advanced labeling techniques, we show that the structure of double‐stranded RNA (dsRNA) changes upon internalization into Xenopus lævis oocytes. Compared to dilute solution, the dsRNA A‐helix is more compact in cells. We recapitulate this compaction in a densely crowded protein solution. Atomic‐resolution molecular dynamics simulations of dsRNA semi‐quantitatively capture the compaction, and identify non‐specific electrostatic interactions between proteins and dsRNA as a possible driver of this effect.