Riboswitches are complex-folded RNAs that function as highly-specific receptors for small molecules. Riboswitches occur naturally in the non-coding regions of many bacterial messenger RNAs, where they function as genetic switches. Specifically, metabolite binding results in the formation of an alternative RNA structure for each riboswitch. These shape changes are harnessed to control gene expression frequently by controlling transcription elongation or by controlling transcription initiation. In one instance, a riboswitch undergoes ribozyme-mediated self-cleavage upon binding to its target metabolite.
Riboswitches share some common features with RNA switches that have been engineered in the laboratory. Previous efforts have produced ribozyme-based switches and even an RNA switch that requires the binding of two ligands. Most recently, a natural riboswitch has been discovered that used two ligand-binding domains to bind two glycine molecules. Together, these domains cooperate to function as a more "digital" genetic switch, thus allowing the organism to control gene expression in response to small changes in the concentration of this amino acid. These results indicate that RNA is a versatile medium for the construction of complex molecular sensors.
Two lines of evidence suggest that riboswitches might be of ancient origin. First, the concentrations of key metabolites such as coenzymes (B12, thiamine pyrophosphate, FMN, SAM), amino acids (lysine, glycine), and nucleobases (guanine and adenine) are recognized by riboswitches. Thus, riboswitches are used to sense compounds that are near universal in their distribution in modern cells. Second, some riboswitches are widely distributed in bacteria, and one class is found in all three domains of life. These characteristics of riboswitches highlight the possibility that they might have originated before the emergence of proteins.
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