Figure 1.

RNA folding pathways and refolding by chaperones. In the absence of chaperones (top), the initial collapse transition produces an ensemble of compact intermediates (I_C) that rearrange to the native structure (N). Because the unfolded RNA contains a mixture of structures, including non-native base pairs (yellow), different subpopulations (U¹, U², U³) fold through different pathways (reviewed in ref. 134). Non-specific collapse transitions lead to kinetically trapped misfolded intermediates (I_mis). Chaperone proteins (C) bind and destabilize RNA folding intermediates, releasing partially unfolded RNAs that can fold again. The structure of the RNA immediately after chaperone release is unknown (question marks).