RNA chaperone StpA loosens interactions of the tertiary structure in the <i>td</i> group I intron in vivo

Waldsich, Christina; Grossberger, Rupert; Schroeder, Renée

doi:10.1101/gad.231302

Cited by 77 publications

(78 citation statements)

References 65 publications

(96 reference statements)

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“…To obtain the very first insights into the mechanism of RNA chaperones, the impact of StpA on the structure of the td intron was assessed in vivo. 53 StpA was found to open the misfolded intron structure by resolving tertiary contacts and in turn reverting the intron conformation to an earlier folding intermediate, giving the RNA another chance to reach the native, splicing-competent state. This destabilizing activity of StpA rendered splicing of td intron mutants with reduced structural stability sensitive to StpA.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

RNA folding in living cells

Zemora

Waldsich

2010

RNA Biology

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Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

RNA folding in living cells

Zemora

Waldsich

2010

RNA Biology

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“…Because spontaneous yield of the native state of large ribozymes even at high Mg 2 + concentrations is small [20], it is likely that in vivo RNA chaperones are required to boost the probability of reaching the folded state within T B . Unlike the well-studied bacterial GroEL-GroES, a well-identified "one-fit-all" chaperonin system for processing cytosolic proteins [23], protein-cofactors that act as RNA chaperones vary from one RNA to the other [24][25][26]. Based on a number of experiments (see [5,27] for reviews) we classify the client RNA molecules into two classes depending on the need for the RNA chaperones to utilize the free energy of ATP hydrolysis in facilitating folding.…”

Section: Classification Of Rna Substratesmentioning

confidence: 99%

Generalized iterative annealing model for the action of RNA chaperones

Hyeon

Thirumalai

2013

The Journal of Chemical Physics

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As a consequence of the rugged landscape of RNA molecules their folding is described by the kinetic partitioning mechanism according to which only a small fraction (φ F ) reaches the folded state while the remaining fraction of molecules is kinetically trapped in misfolded intermediates. The transition from the misfolded states to the native state can far exceed biologically relevant time. Thus, RNA folding in vivo is often aided by protein cofactors, called RNA chaperones, that can rescue RNAs from a multitude of misfolded structures. We consider two models, based on chemical kinetics and chemical master equation, for describing assisted folding. In the passive model, applicable for class I substrates, transient interactions of misfolded structures with RNA chaperones alone are sufficient to destabilize the misfolded structures, thus entropically lowering the barrier to folding. For this mechanism to be efficient the intermediate ribonucleoprotein (RNP) complex between collapsed RNA and protein cofactor should have optimal stability. We also introduce an active model (suitable for stringent substrates with small φ F ), which accounts for the recent experimental findings on the action of CYT-19 on the group I intron ribozyme, showing that RNA chaperones does not discriminate between the misfolded and the native states. In the active model, the RNA chaperone system utilizes chemical energy of ATP hydrolysis to repeatedly bind and release misfolded and folded RNAs, resulting in substantial increase of yield of the native state. The theory outlined here shows, in accord with experiments, that in the steady state the native state does not form with unit probability. * To whom correspondence should be addressed : hyeoncb@kias.re.kr 1 arXiv:1306.3850v1 [q-bio.BM] 17 Jun 2013Since the ground breaking discovery of self-splicing catalytic activity of group I intron ribozymes [1,2] numerous and growing list of cellular functions have been shown to be controlled by RNA molecules [3,4]. These discoveries have made it important to determine how RNA molecules fold [5][6][7], and sometimes switch conformations in response to environmental signals [8] to execute a wide range of activities from regulation of transcription and translation to catalysis. At a first glance, it may appear that RNA folding is simple because of the potential restriction that the four different are paired as demanded by the Watson-Crick (WC) rule. However, there are several factors that make RNA folding considerably more difficult than the more thoroughly investigated protein folding problem [5]. The presence of negative charge on the phosphate group of each nucleotide, participation of a large fraction of nucleotides in non WC base pairing [9], the nearly homopolymeric nature of purine and pyrimidine bases, and paucity of structural data are some of the reasons that render the prediction of RNA structures and their folding challenging [5]. Despite these difficulties considerable progress has been made in understanding how large ribozymes fold i...

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“…A number of RNA-binding proteins and DEAD-box ATPases have the potential to stimulate RNA refolding and strand exchange reactions (Schroeder et al 2004). For example, overexpression of E. coli StpA stimulates splicing of the td group I intron in E. coli and is able to resolve misfolded RNAs as long as the native structure is thermodynamically stable (Waldsich et al 2002;Grossberger et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Self-splicing of a group I intron reveals partitioning of native and misfolded RNA populations in yeast

Jackson¹,

Koduvayur²,

Woodson³

2006

RNA

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Stable RNAs must form specific three-dimensional structures, yet many RNAs become kinetically trapped in misfolded conformations. To understand the factors that control the accuracy of RNA folding in the cell, the self-splicing activity of the Tetrahymena group I intron was compared in different genetic contexts in budding yeast. The extent of splicing was 98% when the intron was placed in its natural rDNA context, but only 3% when the intron was expressed in an exogenous pre-mRNA. Further experiments showed that the probability of forming the active intron structure depends on local sequence context and transcription by Pol I. Pre-rRNAs decayed at similar rates, whether the intron was wild type or inactivated by an internal deletion, suggesting that most of the unreacted pre-rRNA is incompetent to splice. Northern blots and complementation assays showed that mutations that destabilize the intron tertiary structure inhibited self-splicing and processing of internal transcribed spacer 2. The data are consistent with partitioning of pre-rRNAs into active and inactive populations. The misfolded RNAs are sequestered and degraded without refolding to a significant extent. Thus, the initial fidelity of folding can dictate the intracellular fate of transcripts containing this group I intron.

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RNA chaperone StpA loosens interactions of the tertiary structure in the td group I intron in vivo

Cited by 77 publications

References 65 publications

RNA folding in living cells

RNA folding in living cells

Generalized iterative annealing model for the action of RNA chaperones

Self-splicing of a group I intron reveals partitioning of native and misfolded RNA populations in yeast

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