The riboswitch control of gene regulation.

<p>(a) The two full length structures of the <i>tenA</i> thiamine pyrophosphate (TPP, blue oval) riboswitch are shown. Aptamer domain is highlighted in orange solid and broken lines. (b) Simplified diagram of riboswitch folding process for the <i>tenA</i> TPP riboswitch. From 156–171 nt, meta-stable structures (labeled ligand-competent and non-ligand-competent) exchange with one another. From 172–179 nt, ligand (yellow polygon) stabilizes one of the ligand-competent meta-stable structures, thus causing the formation of specific terminator hairpin structures in the full length riboswitch (181–190 nt). The ligand may remain bound or disengage the aptamer later in transcription (polygon in dashed lines in top row, right column). In the absence of ligand (172–179 nt), isomerization to a different structure occurs, causing an antiterminator structure to form downstream (181–190 nt). (c) The energy landscapes of the riboswitch through all three stages of transcription. Each point represents a different secondary structure; marked according to its base pair distance (structure distance) and free energy. Colored stars represent points on the landscape corresponding to structures in (1b). In the energy landscape from 156–171 nt, represented here by the landscape at 165 nt, a small energy barrier and multiple low-energy structures exist on the landscape simultaneously, permitting exchange of meta-stable structures (double arrow). From 172–179 nt (shown for 175 nt), the landscapes are funnel-shaped and cause isomerization to the mfe if ligand is not present to stabilize the ligand-competent structure. From 181–190 nt (shown here for 185 nt), two structures are possible which the RNA may fold into. The high energy barrier between sets precludes switching. Set 1 corresponds to terminator structures and Set 2 corresponds to antiterminator structures. (d) Example calculation of base-pair distance for a simple helix structure.