Riboswitches

Abstract

Riboswitches are messenger RNA domains that regulate gene expression in cis in response to the intracellular concentration of small molecules. In bacteria, they function by controlling transcription or translation and in eukarya, alternative splicing. One bacterial riboswitch that is a small molecule-activated self-cleaving RNA (i.e., a ribozyme) is also known. Riboswitches are a particularly common strategy for gene regulation in Gram-positive bacteria, where they are associated with ~5% of genes. Formally, most riboswitches can be divided into two domains. The aptamer domain is responsible for recognition of the effector small molecule. The sequence of this domain is highly conserved across phylogeny. The expression platform interfaces with the transcription, translation, or splicing machineries. This segment of the riboswitch is often highly variable. Aptamer domains have been discovered that recognize a wide range of metabolites including purines, the amino acids glycine and lysine, the modified sugar glucosamine-6-phosphate, the coenzymes adenosylcobalamin, flavin mononucleotide, thiamine pyrophosphate, and S-adenosylmethionine, as well as the bacterial second messenger cyclic diguanylate. Riboswitches showcase the ability of RNA to recognize small molecules with high affinity and specificity. This, their widespread use in bacteria, and their control of many central metabolic pathways suggest that they may represent an ancient mechanism of gene regulation.