Structure of the S-adenosylmethionine riboswitch regulatory mRNA element

Top Cited Papers
Publisher Website
Google Scholar
Abstract
Genes are commonly turned on or off by protein factors that respond to cellular signals. The recent discovery of riboswitches, regulatory elements within some messenger RNAs, proved that RNA can also detect essential metabolites and control genes. Two structural studies throw new light on the riboswitch system. Serganov et al. use X-ray diffraction to establish the three-dimensional structure of a riboswitch from Escherichia coli bound to its target, a vitamin B1 derivative. These findings reveal how RNA folds to form a precise pocket for its target and how the antibiotic pyrithiamine acts by tricking the riboswitch. This suggests a new drug design strategy for antibacterials and antifungals targeting riboswitches. Montange and Batey have solved the structure of a bacterial riboswitch RNA bound to S-adenosyl methionine. Its complex folded structure reveals how ligand binding leads structural changes that prevent further transcription. 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 directly1,2. 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 cofactors1,2. Here we report the 2.9-Å 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 metabolism3,4,5,6. 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.