Chapter 5 : Small-Molecule-Binding Riboswitches

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Traditionally, the functional role of RNA was thought to be restricted to transferring genetic information from DNA to protein. However, the discovery of RNA elements mediating gene control, chemical reaction catalysis, and signal transduction has changed this perception fundamentally. Its ability to form complex three-dimensional structures that precisely present chemical moieties is imperative in enabling RNA to function as a biological catalyst, regulator, or structural scaffold.

Citation: Lotz T, Suess B. 2019. Small-Molecule-Binding Riboswitches, p 75-88. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0025-2018
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Figure 1

Common mechanism of riboswitches in bacteria. (A) Regulation of translation initiation: In the absence of the ligand, a stem-loop structure is formed between the aptamer domain and a sequence complementary to the Shine-Dalgarno (SD) sequence. Thus, the SD sequence is accessible for 30S binding, and translation initiation occurs. As a consequence of ligand binding (pentagon) and the folding of the aptamer domain, an alternative stem-loop is formed, which sequesters the SD sequence, and the binding of the 30S ribosomal subunit is blocked. (B) Regulation of transcription termination: The aptamer domain is followed by a sequence complementary to the 3′ part of the aptamer and a U stretch. In the absence of the ligand, the complementary 3′ part is base-paired with the aptamer, forming a terminator structure. Thus, RNA polymerase (RNAP) dissociates and transcription is blocked. Upon ligand binding, terminator structure formation is inhibited and transcription can proceed, resulting in expression of the reporter gene.

Citation: Lotz T, Suess B. 2019. Small-Molecule-Binding Riboswitches, p 75-88. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0025-2018
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Image of Figure 2
Figure 2

Structure of the TPP riboswitch. (A) Schematic depiction of the secondary structure of the riboswitch with and without TPP (marked in pink). TPP stabilizes the P1-P1′ helix, which leads to secondary structure changes. The formation of the expression platform follows as a consequence, so that the Shine-Dalgarno (SD) sequence is sequestered in another stem, inhibiting any further gene expression. (B) The X-ray crystal structure of the aptamer bound to TPP (black sticks, center) and Mg ions (black spheres). PDB ID 2GDI ( ); annotations on the structures refer to helices (P) and junctions (J). Adapted from reference with permission.

Citation: Lotz T, Suess B. 2019. Small-Molecule-Binding Riboswitches, p 75-88. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0025-2018
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Table 1

Naturally occurring riboswitches

Citation: Lotz T, Suess B. 2019. Small-Molecule-Binding Riboswitches, p 75-88. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0025-2018

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