Cooperativity, allostery and synergism in ligand binding to riboswitches.

Recent progress in identification and characterization of novel types of non-coding RNAs has proven that RNAs carry out a variety of cellular functions ranging from scaffolding to gene expression control. In both prokaryotic and eukaryotic cells, several classes of non-coding RNAs control expression of dozens of genes in response to specific cues. One of the most interesting and outstanding questions in the RNA field is whether regulatory RNAs are capable of employing basic biological concepts, such as allostery and cooperativity, previously attributed to the function of proteins. Aside from regulatory RNAs that form complementary base pairing with their nucleic acid targets, several RNA classes modulate gene expression via molecular mechanisms which can be paralleled to protein-mediated regulation. Among these RNAs are riboswitches, metabolite-sensing non-coding regulatory elements that adopt intrinsic three-dimensional structures and specifically bind various small molecule ligands. These characteristics of riboswitches make them well-suited for complex regulatory responses observed in allosteric and cooperative protein systems. Here we present an overview of the biochemical, genetic, and structural studies of riboswitches with a major focus on complex regulatory mechanisms and biological principles utilized by riboswitches for such genetic modulation.