FIGURE 6.

Model describing functional role of CR4/5 folding heterogeneity in human telomerase biogenesis. A schematic depicting a hypothetical folding landscape of the hTR CR4/5 domain. Energy valleys represent unique conformations available to CR4/5. The “depth” of a valley is a conceptual proxy for the stability and relative abundance of a particular RNA conformation. In the folding landscape of the “naked” CR4/5 RNA (black line), there exists a diverse ensemble of TWJ conformations with a small contingent of molecules adopting a fold representative of the canonical P6.1 stem (red TWJ). Upon RNP assembly, the CR4/5 folding landscape becomes dominated by one predominant CR4/5 conformation (red line) because of TERT-induced remodeling of the CR4/5 structure.