Predicting loop–helix tertiary structural contacts in RNA pseudoknots

Cao, Song; Giedroc, David P.; Chen, Shi‐Jie

doi:10.1261/rna.1800210

Cited by 40 publications

(50 citation statements)

References 84 publications

(146 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such a structure, containing multiple stemloops, can be stabilized through noncanonical triplex base pairs and coaxial stacking interactions. 6,20–22 Remarkably, in the frameshifting mechanism for translational control of viral protein synthesis (e.g., HIV, SARS and HCV), 7,9,11,14 the ribosome needs to disrupt a downstream pseudoknot in a retroviral RNA to continue the translation with a shifted open reading frame (ORF). This RNA unfolding-regulated mechanism enables expression of different proteins from the same viral RNA genome for virus replication and proliferation.…”

Section: Introductionmentioning

confidence: 99%

Mimicking Ribosomal Unfolding of RNA Pseudoknot in a Protein Channel

Zhang

Yang

et al. 2015

J. Am. Chem. Soc.

Self Cite

View full text Add to dashboard Cite

Pseudoknots are a fundamental RNA tertiary structure with important roles in regulation of mRNA translation. Molecular force spectroscopic approaches such as optical tweezers can track the pseudoknot’s unfolding intermediate states by pulling the RNA chain from both ends, but the kinetic unfolding pathway induced by this method may be different from that in vivo, which occurs during translation and proceeds from the 5′ to 3′ end. Here we developed a ribosome-mimicking, nanopore pulling assay for dissecting the vectorial unfolding mechanism of pseudoknots. The pseudoknot unfolding pathway in the nanopore, either from the 5′ to 3′ end or in the reverse direction, can be controlled by a DNA leader that is attached to the pseudoknot at the 5′ or 3′ ends. The different nanopore conductance between DNA and RNA translocation serves as a marker for the position and structure of the unfolding RNA in the pore. With this design, we provided evidence that the pseudoknot unfolding is a two-step, multistate, metal ion-regulated process depending on the pulling direction. Most notably, unfolding in both directions is rate-limited by the unzipping of the first helix domain (first step), which is Helix-1 in the 5′ → 3′ direction and Helix-2 in the 3′ → 5′ direction, suggesting that the initial unfolding step in either pulling direction needs to overcome an energy barrier contributed by the noncanonical triplex base-pairs and coaxial stacking interactions for the tertiary structure stabilization. These findings provide new insights into RNA vectorial unfolding mechanisms, which play an important role in biological functions including frameshifting.

show abstract

Section: Introductionmentioning

confidence: 99%

Mimicking Ribosomal Unfolding of RNA Pseudoknot in a Protein Channel

Zhang

Yang

et al. 2015

J. Am. Chem. Soc.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Chen's model, favorable for Puzzle 1 and Puzzle 3, involves an interesting multistep procedure. Secondary structure, obtained from Vfold [19,26] is then refined; a coarsegrained nucleotide approach is used to search a conformational dataset for well-known motifs. Further refinement and all atom simulation produce the final conformation.…”

Section: Resultsmentioning

confidence: 99%

“…Similar to Chen's use of Vfold [3,26] to increase accuracy, an energy based secondary structure restraint technique could be used. Given the potential errors in the secondary structure predictions, however, we believe that limited WC base-pairs will provide sufficient restraints that allow our physics based model to predict the 3D structure along with the remaining secondary structure.…”

Section: Discussionmentioning

confidence: 99%

Multiscale modeling of RNA 3D structures

Bell

Xia

Ren

2013

2013 Biomedical Sciences and Engineering Conference (BSEC)

View full text Add to dashboard Cite

Balancing accuracy and computational efficiency while studying biomolecular structures and dynamics necessitates scalable modeling techniques. We have been developing a coarse-grained model for RNA that uses pseudoatoms in place of all-atom representation. By reducing the number of interactions and mean-field representation of environmental effects, significant improvement in computational efficiency is achieved in a comparison to all-atom based physical modeling approaches. A five bead coarse-grained model utilized for RNA 3D structure prediction is presented. Unique features of this framework include the direct mapping between all atom and coarse-grained models, incorporation of electrostatic interactions, continuous and analytical energy function that can be used in molecular dynamics simulations, and statistical derived parameters. Here we present the basic framework of our model and recent applications to RNA folding.

show abstract

“…For example, the pseudo-torsions are used extensively in the VFold model (Fig. 14), which has been used to study RNA folding and stability (Cao & Chen, 2005, 2006; Cao et al . 2010; Tan & Chen, 2008).…”

Section: The η/θ Formalism As Platform For Innovation In Rna Strucmentioning

confidence: 99%

A new way to see RNA

Keating

Humphris

Pyle

2011

Quart. Rev. Biophys.

View full text Add to dashboard Cite

Unlike proteins, the RNA backbone has numerous degrees of freedom (eight, if one counts the sugar pucker), making RNA modeling, structure building and prediction a multidimensional problem of exceptionally high complexity. And yet RNA tertiary structures are not infinite in their structural morphology; rather, they are built from a limited set of discrete units. In order to reduce the dimensionality of the RNA backbone in a physically reasonable way, a shorthand notation was created that reduced the RNA backbone torsion angles to two (η and θ, analogous to ϕ and ψ in proteins). When these torsion angles are calculated for nucleotides in a crystallographic database and plotted against one another, one obtains a plot analogous to a Ramachandran plot (the η/θ plot), with highly populated and unpopulated regions. Nucleotides that occupy proximal positions on the plot have identical structures and are found in the same units of tertiary structure. In this review, we describe the statistical validation of the η/θ formalism and the exploration of features within the η/θ plot. We also describe the application of the η/θ formalism in RNA motif discovery, structural comparison, RNA structure building and tertiary structure prediction. More than a tool, however, the η/θ formalism has provided new insights into RNA structure itself, revealing its fundamental components and the factors underlying RNA architectural form.

show abstract

Predicting loop–helix tertiary structural contacts in RNA pseudoknots

Cited by 40 publications

References 84 publications

Mimicking Ribosomal Unfolding of RNA Pseudoknot in a Protein Channel

Mimicking Ribosomal Unfolding of RNA Pseudoknot in a Protein Channel

Multiscale modeling of RNA 3D structures

A new way to see RNA

Contact Info

Product

Resources

About