The intricate world of riboswitches

Abstract

Riboswitches are segments of the 5'-untranslated region of certain bacterial mRNAs that upon recognition of specific ligands modify the expression of a protein(s) encoded in the message. These proteins are responsible for the biosynthesis or transport of ligands, which are typically organic molecules but could also be metal ions. Riboswitch-mediated control of gene expression might be thermodynamic or kinetic, depending on the rate of transcription elongation by RNA polymerase and the structures adopted by the riboswitch RNA. Certain 5'-untranslated regions harbor two riboswitches in tandem that bind to different ligands. Thus, RNA sensors can respond to metabolic changes by modifying gene expression in ways previously thought to be exclusive of proteins.

Figure 1

Schematic structure of traditional riboswitches (a), which bind single metabolites, and of new riboswitches (b) that can harbor tandem aptamers recognizing different metabolites, (c) where there are no distinct aptamer and expression platform domains, (d) and where Mg²⁺ is the physiological ligand. Aptomer regions are in red and expression platforms in blue.

Figure 2

Flow chart depicting the fate of an elongating mRNA that harbors a riboswitch with a transcription termination mechanism. The aptamer region, synthesized first, is depicted as a blue square. The open shape inside the square represents the metabolite binding pocket. The different shapes reflect various folded conformations of the aptamer, only one of which is competent for binding its ligand. The genetic outcome is determined at two key intersections (highlighted boxes). In order for riboswitch to exert control, both of these events must take place before the polymerase reaches the coding region of the mRNA. Metabolite binding via kinetic or thermodynamic control leads to formation of an intrinsic terminator. Absence of binding prevents formation of the terminator and allows for read-through and expression.