Cooperative Tertiary Interaction Network Guides RNA Folding

Journal Article · Mon Apr 08 04:00:00 EDT 2013 · Cell

DOI:https://doi.org/10.1016/j.cell.2012.01.057· OSTI ID:1039067

Behrouzi, Reza; Roh, Joon Ho; Kilburn, Duncan; Briber, R M; Woodson, Sarah A ^[1]

---

1. JHU

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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: NIHNIST
• OSTI ID: 1039067
• Journal Information: Cell, Journal Name: Cell Journal Issue: (2) ; 04, 2012 Vol. 149; ISSN 0092-8674; ISSN CELLB5
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
HYDROXYL RADICALS
ORIENTATION
RNA
STABILITY