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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:
; ; ; ;  [1];  [2]
  1. (JHU)
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIHNIST
OSTI Identifier:
1039067
Resource Type:
Journal Article
Journal Name:
Cell
Additional Journal Information:
Journal Volume: 149; Journal Issue: (2) ; 04, 2012; Journal ID: ISSN 0092-8674
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; HYDROXYL RADICALS; ORIENTATION; RNA; STABILITY

Citation Formats

Behrouzi, Reza, Roh, Joon Ho, Kilburn, Duncan, Briber, R.M., Woodson, Sarah A., and Maryland). Cooperative Tertiary Interaction Network Guides RNA Folding. United States: N. p., 2013. Web. doi:10.1016/j.cell.2012.01.057.
Behrouzi, Reza, Roh, Joon Ho, Kilburn, Duncan, Briber, R.M., Woodson, Sarah A., & Maryland). Cooperative Tertiary Interaction Network Guides RNA Folding. United States. doi:10.1016/j.cell.2012.01.057.
Behrouzi, Reza, Roh, Joon Ho, Kilburn, Duncan, Briber, R.M., Woodson, Sarah A., and Maryland). Mon . "Cooperative Tertiary Interaction Network Guides RNA Folding". United States. doi:10.1016/j.cell.2012.01.057.
@article{osti_1039067,
title = {Cooperative Tertiary Interaction Network Guides RNA Folding},
author = {Behrouzi, Reza and Roh, Joon Ho and Kilburn, Duncan and Briber, R.M. and Woodson, Sarah A. and Maryland)},
abstractNote = {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.},
doi = {10.1016/j.cell.2012.01.057},
journal = {Cell},
issn = {0092-8674},
number = (2) ; 04, 2012,
volume = 149,
place = {United States},
year = {2013},
month = {4}
}