Fig. 1. Transitions between states (A, B, C) through formation (A to B), disruption (B to A) of a helix (red), and exchange between two helices in A (green) and C (the left/right shoulder of the helix is colored black/green). The relevant pathways labeled along the arrow are shown in the bottom boxes, where the dotted dark lines denote the schematic energy landscape of zipping and tunneling pathways. The unfolding-refolding pathway are shown with gray color, U is the unfolded, open chain.

Fig. 2. The main pathways of HDV ribozyme under two different scenarios: refolding (a) and co-transcriptional folding (b). Upper and lowercase letters denote the ribozyme region and the flanking region. The unpaired nucleotides in the external loop are simply described by dotted lines in panel (a). The rate-limited transition in the slow refolding pathway panel (a) and the main co-transcriptional transition with net flux about 90% (b) are shown with red and green arrows respectively. Except the different RNA lengths in panels (a) and (b), structure model of states denoted inside and outside parentheses in panel (b) are the same.

Fig. 3. The co-transcriptional folding behaviors of the yjdF riboswitch from B. subtilis. The population kinetics of main states and their structure at an elongation rate of 15 nt/s are shown in (a) with 0-μM and (b) with 10-μM ligand. Important folding events are mapped in the low panel. The superscript “b” denotes the corresponding state with ligand bound. C0 is the open chain and C4 is a four-way branch structure shown in box near C5. Structures C1, C2, and C3 composed of one or more hairpins labeled in the brackets nearby. The RBS region is colored pink.

Fig. 4. Structure transitions on main co-transcriptional folding pathways of the pbuE riboswitch. T is the terminator hairpin. Nucleotides within helix regions of the aptamer structure and the pause site are colored differently.

Fig. 5. Regulatory behaviors of the TPP (a) and S_MK riboswitch (b). The nature ligand of S_MK riboswitch is S-adenosylmethionine (SAM). The arrows with dotted lines denote the co-transcriptional folding, where RNAs transit from a series of intermediate states (not shown) to ON state, which is formed near the end of transcription. The 5’ splice site in the TPP riboswitch (a) and the SD in the S_MK riboswitch are colored red. The 5’ ends of nascent RNA are shown with red circles.