title: A guanosine-centric mechanism for RNA chaperone function.
abstract: RNA chaperones are ubiquitous, heterogeneous proteins essential for RNA structural biogenesis and function. We investigated the mechanism of chaperone-mediated RNA folding by following the time-resolved dimerization of the packaging domain of a retroviral RNA at nucleotide resolution. In the absence of the nucleocapsid (NC) chaperone, dimerization proceeded through multiple, slow-folding intermediates. In the presence of NC, dimerization occurred rapidly through a single structural intermediate. The RNA binding domain of heterogeneous nuclear ribonucleoprotein A1 protein, a structurally unrelated chaperone, also accelerated dimerization. Both chaperones interacted primarily with guanosine residues. Replacing guanosine with more weakly pairing inosine yielded an RNA that folded rapidly without a facilitating chaperone. These results show that RNA chaperones can simplify RNA folding landscapes by weakening intramolecular interactions involving guanosine and explain many RNA chaperone activities.
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, USA.
authors.forename: Jacob K
authors.initials: JK
authors.lastname: Grohman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gorelick
authors.forename: Colin R
authors.initials: CR
authors.lastname: Lickwar
authors.forename: Jason D
authors.initials: JD
authors.lastname: Lieb
authors.forename: Brian D
authors.initials: BD
authors.lastname: Bower
authors.forename: Brent M
authors.initials: BM
authors.lastname: Znosko
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Weeks
mesh_terms: D001483:Base Sequence; D019281:Dimerization; D006151:Guanosine / Q000737:chemistry / Q000378:metabolism*; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000737:chemistry / Q000378:metabolism; D007288:Inosine / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D019590:Nucleocapsid Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D018832:Molecular Chaperones; D019590:Nucleocapsid Proteins; D012367:RNA, Viral; D006151:Guanosine; D007288:Inosine