Recent insights on RNA folding mechanisms from catalytic RNA.

Methods for probing RNA structure in real time have revealed that initial folding steps are complete in less than a second. Refolding of large catalytic RNAs in vitro often results in long-lived intermediates that reach the native structure very slowly. These kinetically trapped intermediates arise from alternative secondary structures that form early in the folding process. In cells, proteins modulate the outcome of RNA folding reactions by stabilizing specific conformations or by accelerating refolding of misfolded intermediates. At the same time, competition between metastable conformations provides a means for regulating the biological activity of transcripts.