title: An integrated perspective on RNA aptamer ligand-recognition models: clearing muddy waters.
abstract: Riboswitches are short RNA motifs that sensitively and selectively bind cognate ligands to modulate gene expression. Like protein receptor-ligand pairs, their binding dynamics are traditionally categorized as following one of two paradigmatic mechanisms: conformational selection and induced fit. In conformational selection, ligand binding stabilizes a particular state already present in the receptor's dynamic ensemble. In induced fit, ligand-receptor interactions enable the system to overcome the energetic barrier into a previously inaccessible state. In this article, we question whether a polarized division of RNA binding mechanisms truly meets the conceptual needs of the field. We will review the history behind this classification of RNA-ligand interactions, and the way induced fit in particular has been rehabilitated by single-molecule studies of RNA aptamers. We will highlight several recent results from single-molecule experimental studies of riboswitches that reveal gaps or even contradictions between common definitions of the two terms, and we will conclude by proposing a more robust framework that considers the range of RNA behaviors unveiled in recent years as a reality to be described, rather than an increasingly unwieldy set of exceptions to the traditional models.
authors.affiliation: Department of Physics and Astronomy, University of St. Andrews, St. Andrews, KY16 9SS, UK. km855@st-andrews.ac.uk.
authors.forename: K
authors.initials: K
authors.lastname: McCluskey
authors.affiliation: Department of Physics and Astronomy, University of St. Andrews, St. Andrews, KY16 9SS, UK. km855@st-andrews.ac.uk and Biomolecular Sciences Research Complex, University of St. Andrews, St. Andrews, KY16 9SS, UK. jcp10@st-andrews.ac.uk.
authors.forename: J
authors.identifier: http://orcid.org/0000-0002-5807-5385
authors.initials: J
authors.lastname: Carlos Penedo
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000378:metabolism; D064267:Intrinsically Disordered Proteins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D058928:Riboswitch
chemical_list: D052157:Aptamers, Nucleotide; D064267:Intrinsically Disordered Proteins; D008024:Ligands; D058928:Riboswitch; D012313:RNA