Single-molecule RNA folding

Single-molecule experiments significantly expand our capability to characterize complex dynamics of biological processes. This relatively new approach has contributed significantly to our understanding of the RNA folding problem. Recent single-molecule experiments, together with structural and biochemical characterizations of RNA at the ensemble level, show that RNA molecules typically fold across a highly rugged energy landscape. As a result, long-lived folding intermediates, multiple folding pathways, and heterogeneous conformational dynamics are commonly found for RNA enzymes. While initial results have suggested that stable secondary structures are partly responsible for the rugged energy landscape of RNA, a complete mechanistic understanding of the complex folding behavior has not yet been obtained. A combination of single-molecule experiments, which are well suited to analyze transient and heterogeneous dynamic behaviors, with ensemble characterizations that can provide structural information at a superior resolution will likely provide more answers.