title: Cooperative tertiary interaction network guides RNA folding.
abstract: Noncoding RNAs form unique 3D structures, which perform many regulatory functions. To understand how RNAs fold uniquely despite a small number of tertiary interaction motifs, we mutated the major tertiary interactions in a group I ribozyme by single-base substitutions. The resulting perturbations to the folding energy landscape were measured using SAXS, ribozyme activity, hydroxyl radical footprinting, and native PAGE. Double- and triple-mutant cycles show that most tertiary interactions have a small effect on the stability of the native state. Instead, the formation of core and peripheral structural motifs is cooperatively linked in near-native folding intermediates, and this cooperativity depends on the native helix orientation. The emergence of a cooperative interaction network at an early stage of folding suppresses nonnative structures and guides the search for the native state. We suggest that cooperativity in noncoding RNAs arose from natural selection of architectures conducive to forming a unique, stable fold.
authors.affiliation: T.C. Jenkins Department of Biophysics, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Reza
authors.initials: R
authors.lastname: Behrouzi
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Roh
authors.forename: Duncan
authors.initials: D
authors.lastname: Kilburn
authors.forename: R M
authors.initials: RM
authors.lastname: Briber
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Woodson
mesh_terms: D020627:Azoarcus / Q000201:enzymology* / Q000235:genetics*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs; D059370:RNA Folding; D016337:RNA, Catalytic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053838:Scattering, Small Angle; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: C116167:GIR1 ribozyme; D016337:RNA, Catalytic