title: Conformational capture of the SAM-II riboswitch.
abstract: Riboswitches are gene regulation elements in mRNA that function by specifically responding to metabolites. Although the metabolite-bound states of riboswitches have proven amenable to structure determination efforts, knowledge of the structural features of riboswitches in their ligand-free forms and their ligand-response mechanisms giving rise to regulatory control is lacking. Here we explore the ligand-induced folding process of the S-adenosylmethionine type II (SAM-II) riboswitch using chemical and biophysical methods, including NMR and fluorescence spectroscopy, and single-molecule fluorescence imaging. The data reveal that the unliganded SAM-II riboswitch is dynamic in nature, in that its stem-loop element becomes engaged in a pseudoknot fold through base-pairing with nucleosides in the 3' overhang containing the Shine-Dalgarno sequence. Although the pseudoknot structure is highly transient in the absence of its ligand, S-adenosylmethionine (SAM), it becomes conformationally restrained upon ligand recognition, through a conformational capture mechanism. These insights provide a molecular understanding of riboswitch dynamics that shed new light on the mechanism of riboswitch-mediated translational regulation.
authors.affiliation: Institute of Organic Chemistry, Center for Molecular Biosciences, University of Innsbruck, Innsbruck, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Haller
authors.forename: Ulrike
authors.initials: U
authors.lastname: Rieder
authors.forename: Michaela
authors.initials: M
authors.lastname: Aigner
authors.forename: Scott C
authors.initials: SC
authors.lastname: Blanchard
authors.forename: Ronald
authors.initials: R
authors.lastname: Micura
mesh_terms: D020029:Base Pairing; D031541:Fluorescence Resonance Energy Transfer; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008856:Microscopy, Fluorescence; D009690:Nucleic Acid Conformation; D012329:RNA, Bacterial / Q000737:chemistry*; D058928:Riboswitch / Q000187:drug effects; D012436:S-Adenosylmethionine / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
chemical_list: D008024:Ligands; D012329:RNA, Bacterial; D058928:Riboswitch; D012436:S-Adenosylmethionine