Structure and mechanism of the T-box riboswitches

In most Gram‐positive bacteria, including many clinically devastating pathogens from genera such as Bacillus, Clostridium, Listeria, and Staphylococcus, T‐box riboswitches sense and regulate intracellular availability of amino acids through a multipartite messenger RNA (mRNA)–transfer RNA (tRNA) interaction. The T‐box mRNA leaders respond to nutrient starvation by specifically binding cognate tRNAs and sensing whether the bound tRNA is aminoacylated, as a proxy for amino acid availability. Based on this readout, T‐boxes direct a transcriptional or translational switch to control the expression of downstream genes involved in various aspects of amino acid metabolism: biosynthesis, transport, aminoacylation, transamidation, and so forth. Two decades after its discovery, the structural and mechanistic underpinnings of the T‐box riboswitch were recently elucidated, producing a wealth of insights into how two structured RNAs can recognize each other with robust affinity and exquisite selectivity. The T‐box paradigm exemplifies how natural noncoding RNAs can interact not just through sequence complementarity but can add molecular specificity by precisely juxtaposing RNA structural motifs, exploiting inherently flexible elements and the biophysical properties of post‐transcriptional modifications, ultimately achieving a high degree of shape complementarity through mutually induced fit. The T‐box also provides a proof‐of‐principle that compact RNA domains can recognize minute chemical changes (such as tRNA aminoacylation) on another RNA. The unveiling of the structure and mechanism of the T‐box system thus expands our appreciation of the range of capabilities and modes of action of structured noncoding RNAs, and hints at the existence of networks of noncoding RNAs that communicate through both, structural and sequence specificity. WIREs RNA 2015, 6:419–433. doi: 10.1002/wrna.1285 This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs Regulatory RNAs/RNAi/Riboswitches > Riboswitches