title: Riboswitch function: flipping the switch or tuning the dimmer?
abstract: Riboswitches are structured mRNA elements involved in gene regulation that respond to the intracellular concentration of specific small molecules. Binding of their cognate ligand is thought to elicit a global conformational change of the riboswitch, in addition to modulating the fine structure of the binding site. X-ray crystallography has produced detailed descriptions of the three-dimensional structures of the ligand-bound conformations of several riboswitches. We have employed small-angle X-ray scattering (SAXS) to generate low-resolution reconstructions of the ligand-free states of the ligand-binding domains of riboswitches that respond to thiamine pyrophosphate (TPP), and cyclic diguanylate (c-di-GMP), a bacterial second messenger. Comparison of the SAXS reconstructions with the crystal structures of these two riboswitches demonstrates that the RNAs undergo dramatic ligand-induced global conformational changes. However, this is not an universal feature of riboswitches. SAXS analysis of the solution behavior of several other riboswitch ligand-binding domains demonstrates a broad spectrum of conformational switching behaviors, ranging from the unambiguous switching of the TPP and c-di-GMP riboswitches to complete lack of switching for the flavin mononucleotide (FMN) riboswitch. Moreover, the switching behavior varies between examples of the same riboswitch from different organisms. The range of observed behaviors suggests that in response to the evolutionary need for precise genetic regulation, riboswitches may be tuned to function more as dimmers or rheostats than binary on/off switches.
authors.affiliation: Howard Hughes Medical Institute, USA.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Baird
authors.forename: Nadia
authors.initials: N
authors.lastname: Kulshina
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Ferré-D'Amaré
mesh_terms: D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012333:RNA, Messenger / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D058928:Riboswitch / Q000235:genetics / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D058928:Riboswitch
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