Role of counterion condensation in folding of the Tetrahymena ribozyme. I. Equilibrium stabilization by cations

Heilman-Miller, Susan L.; Thirumalai, D.; Woodson, Sarah A.

doi:10.1006/jmbi.2001.4437

Cited by 180 publications

(251 citation statements)

References 47 publications

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“…16 Similarly, we showed, using experiments and simulations, that when the ribozyme was refolded in polyamines, small multivalent polyamines stabilized the folded RNA more effectively than large diamines or ammonium ion. 17 Because the hydration chemistry of polyamines does not change significantly with their size, it is unlikely that such effects are due to bond energy or coordination geometry.…”

Section: Introductionmentioning

confidence: 83%

Charge Density of Divalent Metal Cations Determines RNA Stability

et al. 2007

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RNA molecules are exquisitely sensitive to the properties of counterions. The folding equilibrium of the Tetrahymena ribozyme is measured by non-denaturing gel electrophoresis in the presence of divalent group IIA metal cations. The stability of the folded ribozyme increases with the charge density (ζ) of the cation. Similar scaling is found when the free energy of the RNA folded in small and large metal cations is measured by urea denaturation. Brownian dynamics simulations of a polyelectrolyte show that the experimental observations can be explained by non-specific ion-RNA interactions in the absence of site-specific metal chelation. The experimental and simulation results establish that RNA stability is largely determined by a combination of counterion charge and the packing efficiency of condensed cations that depends on the excluded volume of the cations.

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Section: Introductionmentioning

confidence: 83%

Charge Density of Divalent Metal Cations Determines RNA Stability

et al. 2007

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“…Most simply, helices at low ionic concentrations repel; at higher ionic concentration, this repulsion is reduced due to the enhanced screening, allowing helices to approach one another (Figure 2A). However, some have proposed the existence of attractive forces in polyelectrolyte systems under certain ionic conditions that may be responsible for the coalescence of helices in the folded state [59,60].…”

Section: Simple Forces Underlying the Complex Behavior Of Rnamentioning

confidence: 99%

Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

Chu

Herschlag

2008

Current Opinion in Structural Biology

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SummaryThe rapid development of our understanding of the diverse biological roles fulfilled by non-coding RNA has motivated interest in the basic macromolecular behavior, structure, and function of RNA. We focus on two areas in the behavior of complex RNAs. First, we present advances in the understanding of how RNA folding is accomplished in vivo by presenting a mechanism for the action of DEAD-box proteins. Members of this family are intimately associated with almost all cellular processes involving RNA, mediating RNA structural rearrangements and chaperoning their folding. Next, we focus on advances in understanding and characterizing the basic biophysical forces that govern the folding of complex RNAs. Ultimately we expect that a confluence and synergy between these approaches will lead to profound understanding of RNA and its biology.The explosion in our knowledge about noncoding RNA (ncRNA) -RNA that is not translated into protein -has expanded interest in RNA beyond the traditional RNA community. Diverse ncRNAs include the recently-discovered riboswitches, whose novel gene-regulation function is induced by the binding of small metabolites [1]; most of the so-called "Human Accelerated Regions" (HAR) of the human genome, whose recent evolution may be linked to the emergence of the human brain [2]; and many ncRNAs of unknown function [3]. These discoveries underscore the need to understand the fundamental macromolecular behavior of RNA, its structure and dynamics, and how these RNAs are handled and exploited in biology.Study of catalytic RNAs, which allow detection of correct folding via activity measurements, has established basic thermodynamic and kinetic properties of RNA folding. Large catalytic RNAs such as the group I intron from Tetrahymena thermophila and the RNase P RNA from Bacillus subtilis fold at vastly different rates under different conditions upon addition of Mg 2+ and have been shown to fold via multiple parallel pathways, in which different molecules follow different routes with different rates and intermediates, to a common final folded structure [4,5]. These observations support the common view that RNAs traverse rugged energy landscapes as they fold [6,7]. However, little is known about the true shape of these

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“…Moreover, recent studies have shown valence, size, and shape of counterions profoundly influence RNA folding. [147][148][149][150][151] Despite the complexity, it is possible to devise physics-based models that capture the essential aspects of RNA folding and dynamics. In order to provide a framework for understanding and anticipating the outcomes of increasingly sophisticated experiments involving RNA we have developed two classes of models.…”

Section: Rna Foldingmentioning

confidence: 99%

Minimal Models for Proteins and RNA: From Folding to Function

Pincus

Cho

Hyeon

et al. 2008

Progress in Molecular Biology and Translational Science

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We present a panoramic view of the utility of coarse-grained (CG) models to study folding and functions of proteins and RNA. Drawing largely on the methods developed in our group over the last twenty years, we describe a number of key applications ranging from folding of proteins with disulfide bonds to functions of molecular machines. After presenting the theoretical basis that justifies the use of CG models, we explore the biophysical basis for the emergence of a finite number of folds from lattice models. The lattice model simulations of approach to the folded state show that non-native interactions are relevant only early in the folding process -a finding that rationalizes the success of structure-based models that emphasize native interactions. Applications of off-lattice C α and models that explicitly consider side chains (C α -SCM) to folding of β-hairpin and effects of macromolecular crowding are briefly discussed. Successful applications of a new class of off-lattice models, referred to as the Self- We also present two distinct models for RNA, namely, the Three Site Interaction (TIS) model and the SOP model, that probe forced unfolding and force quench refolding of a simple hairpin and Azoarcus ribozyme. The unfolding pathways of Azoarcus ribozyme depend on the loading rate, while constant force and constant loading rate simulations of the hairpin show that both forced-unfolding and force-quench refolding pathways are heterogeneous. The location of the transition state moves as force is varied. The predictions based on the SOP model show that force-induced unfolding pathways of the ribozyme can be dramatically changed by varying the loading rate. We conclude with a discussion of future prospects for the use of coarse-grained models in addressing problems of outstanding interest in biology.

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Role of counterion condensation in folding of the Tetrahymena ribozyme. I. Equilibrium stabilization by cations

Cited by 180 publications

References 47 publications

Charge Density of Divalent Metal Cations Determines RNA Stability

Charge Density of Divalent Metal Cations Determines RNA Stability

Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

Minimal Models for Proteins and RNA: From Folding to Function

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