The bacterial yjdF riboswitch regulates translation through its tRNA-like fold

Unlike most riboswitches, which have one cognate effector, the bacterial yjdF riboswitch binds to diverse azaaromatic compounds, only a subset of which cause it to activate translation. We examined the yjdF aptamer domain by small-angle X-ray scattering and found that in the presence of activating ligands, the RNA adopts an overall shape similar to that of tRNA. Sequence analyses suggested that the yjdF aptamer is a homolog of tRNA, and that two of the conserved loops of the riboswitch are equivalent to the D-loop and T-loop of tRNA, associating to form an elbow-like tertiary interaction. Chemical probing indicated that this association is promoted by activating ligands such as chelerythrine and harmine. In its native mRNA context, activator ligands stabilize the tRNA-like fold of the yjdF aptamer, outcompeting the attenuated state in which its T-loop base pairs to the Shine-Dalgarno element of the mRNA. Moreover, we demonstrate that the liganded aptamer itself activates translation, as authentic tRNAs, when grafted into mRNA, can potently activate translation. Taken together, our data demonstrate the ability of tRNA to function as a small-molecule responsive cis regulatory element.