Unraveling the structural complexity in a single-stranded RNA tail: implications for efficient ligand binding in the prequeuosine riboswitch

Eichhorn, Catherine D.; Feng, Jun; Suddala, Krishna C.; Walter, Nils G.; Brooks, Charles L.; Al-Hashimi, Hashim M.

One of the main questions we set out to explore during the course of our studies was how the queC aptamer manages to efficiently bind its cognate ligand despite the small commitment time available in the kinetic switch and the large conformational space that may be available to a highly disordered ssRNA, which would have to search many competing conformations before arriving at the ligand bound pseudoknot conformation. Our study reveals that the ssRNA is not entirely disordered, but rather, has the character of a stacked A-form-like helical conformation which may effectively reduce the conformational search of the ssRNA, promoting efficient docking onto the hairpin to form the pseudoknot. Moreover, our study uncovers a greater degree of flexibility towards the terminal ends, particularly the 5 0 -end which forms the pivot point for docking the ssRNA tail onto the hairpin.