A Guanosine-Centric Mechanism for RNA Chaperone Function

• Published in: Science (American Association for the Advancement of Science) Vol. 340; no. 6129; pp. 190 - 195
• Main Authors: Grohman, Jacob K., Gorelick, Robert J., Lickwar, Colin R., Lieb, Jason D., Bower, Brian D., Znosko, Brent M., Weeks, Kevin M.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 12.04.2013; The American Association for the Advancement of Science
• Subjects: Base Sequence; Biochemistry; Dimerization; Dimers; Genomes; Guanosine - chemistry; Guanosine - metabolism; Heterogeneous Nuclear Ribonucleoprotein A1; Heterogeneous nuclear ribonucleoproteins; Heterogeneous-Nuclear Ribonucleoprotein Group A-B - chemistry; Heterogeneous-Nuclear Ribonucleoprotein Group A-B - metabolism; Inosine - chemistry; Inosine - metabolism; Kinetics; Models, Molecular; Molecular biology; Molecular Chaperones - chemistry; Molecular Chaperones - metabolism; Moloney murine leukemia virus; Moloney murine leukemia virus - genetics; Moloney murine leukemia virus - metabolism; Monomers; Nucleic Acid Conformation; Nucleocapsid Proteins - chemistry; Nucleocapsid Proteins - metabolism; Nucleotides; Protein Binding; Protein folding; Reactivity; RNA; RNA, Viral - chemistry; RNA, Viral - metabolism; RNA-protein interactions
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1230715

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.