title: Visualizing transient low-populated structures of RNA.
abstract: The visualization of RNA conformational changes has provided fundamental insights into how regulatory RNAs carry out their biological functions. The RNA structural transitions that have been characterized so far involve long-lived species that can be captured by structure characterization techniques. Here we report the nuclear magnetic resonance visualization of RNA transitions towards 'invisible' excited states (ESs), which exist in too little abundance (2-13%) and for too short a duration (45-250 μs) to allow structural characterization by conventional techniques. Transitions towards ESs result in localized rearrangements in base-pairing that alter building block elements of RNA architecture, including helix-junction-helix motifs and apical loops. The ES can inhibit function by sequestering residues involved in recognition and signalling or promote ATP-independent strand exchange. Thus, RNAs do not adopt a single conformation, but rather exist in rapid equilibrium with alternative ESs, which can be stabilized by cellular cues to affect functional outcomes.
authors.affiliation: Department of Chemistry & Biophysics, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109-1055, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Dethoff
authors.forename: Katja
authors.initials: K
authors.lastname: Petzold
authors.forename: Jeetender
authors.initials: J
authors.lastname: Chugh
authors.forename: Anette
authors.initials: A
authors.lastname: Casiano-Negroni
authors.forename: Hashim M
authors.initials: HM
authors.lastname: Al-Hashimi
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D012367:RNA, Viral