Riboswitches: natural SELEXion

Advances in our knowledge of the structure and chemistry of RNA have been harnessed in the process known as SELEX to develop artificial RNA-based molecules that can act as enzymes and ligand binders performing a wide variety of functions. The discovery of riboswitches, natural RNA aptamers involved in genetic regulation, offers a basis of comparison between the artificial selection and the natural selection of structured RNAs for smallmolecule recognition. The guanine riboswitch structural determination allows us to draw conclusions regarding the apparent increased complexity of the riboswitch aptamers compared to their in-vitro-selected cousins. Received 1 August 2005; received after revision 22 August 2005; accepted 2 September 2005     

Structure of the S-adenosylmethionine riboswitch regulatory mRNA element

Riboswitches are cis-acting genetic regulatory elements found in the 5'-untranslated regions of messenger RNAs that control gene expression through their ability to bind small molecule metabolites directly. Regulation occurs through the interplay of two domains of the RNA: an aptamer domain that responds to intracellular metabolite concentrations and an expression platform that uses two mutually exclusive secondary structures to direct a decision-making process. In Gram-positive bacteria such as Bacillus species, riboswitches control the expression of more than 2% of all genes through their ability to respond to a diverse set of metabolites including amino acids, nucleobases and protein cofactors. Here we report the 2.9-angstroms resolution crystal structure of an S-adenosylmethionine (SAM)-responsive riboswitch from Thermoanaerobacter tengcongensis complexed with S-adenosylmethionine, an RNA element that controls the expression of several genes involved in sulphur and methionine metabolism. This RNA folds into a complex three-dimensional architecture that recognizes almost every functional group of the ligand through a combination of direct and indirect readout mechanisms. Ligand binding induces the formation of a series of tertiary interactions with one of the helices, serving as a communication link between the aptamer and expression platform domains.