Compaction of RNA Duplexes in the Cell

The structure and flexibility of RNA depend sensitively on the microenvironment. Using pulsed electron-electron double-resonance (PELDOR) 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 capture semi-quantitatively the compaction, and identify non-specific electrostatic interactions between proteins and dsRNA as a possible driver of this effect.