How Does the ykkCD Sensor Exert Its Function?


The ykkCD RNA sensor is a riboswitch. Riboswitches are conserved elements in the mRNA that regulate gene expression by allosteric structural changes. They are located in the 5’ untranslated region (5’UTR) of the gene they regulate. Most riboswitches characterized to date turn off expression of a metabolite-producing gene once sufficient amounts of metabolite is synthesized. As metabolite concentration reaches a threshold, it is able to bind to the riboswitch and initiate a structural change in the mRNA that prevents expression of the metabolite-producing gene either by halting transcription or preventing protein synthesis.

The main difference between gene expression regulation by riboswitches and regulation by transcription factors is that riboswitches are part of the mRNA and are able to directly bind to their target ligand without the help of a protein cofactor. How does the ykkCD sensor undergo structural change upon tetracycline binding and directs expression of the ykkCD efflux pump? (A) In the absence of tetracycline the ykkCD sensor RNA folds into a structure that contains a terminator stem.

This stem prevents synthesis of the ykkCD efflux pump mRNA. As a result the efflux pump is not made. (B) In the presence of tetracycline the ykkCD RNA sensor folds into a structure that does not contain the terminator stem. As a result the ykkCD efflux pump is made and able to pump tetracycline out of the cells (Fig. 1.3).


Figure 1.3: A model depicting the conformational change of the ykkCD toxin sensor upon tetracycline binding. When tetracycline levels rise to a critical threshold the ykkCD sensor binds to tetracycline and undergoes a structural change that permits production of the MDR pump.


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