Catalytic activity as a probe of native RNA folding

As RNAs fold to functional structures, they traverse complex energy landscapes that include many partially folded and misfolded intermediates. For structured RNAs that possess catalytic activity, this activity can provide a powerful means of monitoring folding that is complementary to biophysical approaches. RNA catalysis can be used to track accumulation of the native RNA specifically and quantitatively, readily distinguishing the native structure from intermediates that resemble it and may not be differentiated by other approaches. Here, we outline how to design and interpret experiments using catalytic activity to monitor RNA folding, and we summarize adaptations of the method that have been used to probe aspects of folding well beyond determination of the folding rates.