The glmS Riboswitch Integrates Signals from Activating and Inhibitory Metabolites In Vivo

The glmS riboswitch belongs to the family of regulatory RNAs that provide feedback regulation of metabolic genes. It is also a ribozyme that self-cleaves upon binding glucosamine-6-phosphate, the product of the enzyme encoded by glmS. The ligand concentration dependence of intracellular self-cleavage kinetics was measured for the first time in a yeast model system and surprisingly revealed that this riboswitch is subject to inhibition as well as activation by hexose metabolites. Reporter gene experiments in B. subtilis confirmed that this riboswitch integrates positive and negative chemical signals in its natural biological context. Contrary to the conventional view that a riboswitch responds to just a single cognate metabolite, our new model proposes that a single riboswitch integrates information from an array of chemical signals to modulate gene expression according to the overall metabolic state of the cell. The glmS riboswitch belongs to the family of regulatory RNAs that provide feedback regulation of metabolic genes1–4. Most riboswitches are found in the 5 ′ untranslated regions of mRNAs that encode metabolic genes, where they control gene expression by adopting alternative RNA structures in the presence and absence of small ligands. Extensive studie