Small-Molecule-Binding Riboswitches.

RNA is a versatile biomolecule capable of transferring information, taking on distinct three-dimensional shapes, and reacting to ambient conditions. RNA molecules utilize a wide range of mechanisms to control gene expression. An example of such regulation is riboswitches. Consisting exclusively of RNA, they are able to control important metabolic processes, thus providing an elegant and efficient RNA-only regulation system. Existing across all domains of life, riboswitches appear to represent one of the most highly conserved mechanisms for the regulation of a broad range of biochemical pathways. Through binding of a wide range of small-molecule ligands to their so-called aptamer domain, riboswitches undergo a conformational change in their downstream "expression platform." In consequence, the pattern of gene expression changes, which in turn results in increased or decreased protein production. Riboswitches unite the sensing and transduction of a signal that can directly be coupled to the metabolism of the cell; thus they constitute a very potent regulatory mechanism for many organisms. Highly specific RNA-binding domains not only occur in vivo but can also be evolved by means of the SELEX (systematic evolution of ligands by exponential enrichment) method, which allows in vitro selection of aptamers against almost any ligand. Coupling of these aptamers with an expression platform has led to the development of synthetic riboswitches, a highly active research field of great relevance and immense potential. The aim of this review is to summarize developments in the riboswitch field over the last decade and address key questions of recent research.