doi:10.1016/j.sbi.2005.05.003 
Copyright © 2005 Elsevier Ltd All rights reserved.
Riboswitches as versatile gene control elements
Brian J Tucker1 and Ronald R Breaker2, 
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
2Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, CT 06520, USA
Available online 24 May 2005.
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Riboswitches are structured elements typically found in the 5′ untranslated regions of mRNAs, where they regulate gene expression by binding to small metabolites. In all examples studied to date, these RNA control elements do not require the involvement of protein factors for metabolite binding. Riboswitches appear to be pervasive in eubacteria, suggesting that this form of regulation is an important mechanism by which metabolic genes are controlled. Recently discovered riboswitch classes have surprisingly complex mechanisms for regulating gene expression and new high-resolution structural models of these RNAs provide insight into the molecular details of metabolite recognition by natural RNA aptamers.
Figure 1. Common mechanisms of riboswitch gene control. Transcription control involves metabolite binding and stabilization of a specific conformation of the aptamer domain that precludes formation of a competing anti-terminator stem. This allows formation of a terminator stem, which prevents the full-length mRNA from being synthesized. In contrast, control of translation is accomplished by metabolite-induced structural changes that sequester the ribosome-binding site (RBS), thereby preventing the ribosome from binding to the mRNA.
Figure 2. Recently characterized riboswitch classes. (a) Adenine riboswitch (ydhL). In contrast to previously characterized riboswitches, binding of adenine promotes mRNA transcription by preventing formation of a terminator stem. (b) GlcN6P riboswitch (glmS). Binding of GlcN6P induces the riboswitch to self-cleave (site identified by arrow). RNA cleavage results in decreased gene expression through an unknown mechanism. (c) Glycine riboswitch (gcvT). Binding of glycine allows mRNA transcription using a mechanism similar to that of the adenine riboswitch. However, two glycine molecules are bound cooperatively to two aptamer domains (labeled I and II). The sequence that forms the terminator stem is shaded.
Figure 3. Structural features of the purine-responsive riboswitch aptamers. Structures of (a) the guanine riboswitch aptamer (xpt-pbuX) and (b) the adenine riboswitch aptamer (add) reveal a similar tertiary fold, despite only 59% sequence identity. Bound metabolites, hypoxanthine (Hpa) and adenine (Ade), respectively, are shown in red. Discrimination at the binding site of the guanine aptamer (c,d) and the adenine aptamer (e) results from the identity of nucleotide 74 (using the numbering system of the B. subtilis construct), which makes Watson–Crick hydrogen bonds to the appropriate metabolite. Nucleotides U22, U47 and U51 are colored orange, magenta and yellow, respectively. The oxygen and nitrogen atoms of the metabolite and nucleotide 74 are colored red and blue, respectively.
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