Correction to NMR of CCCC RNA Reveals a Right-Handed Helix and Revised Parameters for AMBER Force Field Torsions Improve Structural Predictions from Molecular Dynamics

Tubbs, Jason D.; Condon, David E.; Kennedy, Scott D.; Hauser, Melanie; Bevilacqua, Philip C.; Turner, Douglas H.

doi:10.1021/bi400401j

Cited by 3 publications

(2 citation statements)

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“…Generally, base-paired nucleotides are supposed to show low (near zero) reactivity values ( Weidmann et al 2021 ). Most of the lower reactivity is observed for sequential cytosines, possibly caused by stacking of the single-stranded region ( Tubbs et al 2013 ), and confirmed by our nine cytosine-containing control; however, our NMR data indicates a flexible loop, shown by mixed sugar puckers ( Supplemental Fig. S2 ).…”

Section: Resultssupporting

confidence: 75%

RNA:RNA interaction in ternary complexes resolved by chemical probing

Banijamali

Baronti

Becker

et al. 2022

RNA

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RNA regulation can be performed by a second targeting RNA molecule, such as in the microRNA regulation mechanism. Selective 2’-hydroxyl acylation analyzed by primer extension (SHAPE) probes structure of RNA molecules and can resolve RNA:protein interactions, but RNA:RNA interactions have not yet been addressed with this technique. Here, we apply SHAPE to investigate RNA-mediated binding processes in RNA:RNA and RNA:RNA-RBP complexes. We use RNA:RNA binding by SHAPE (abbreviated RABS) to investigate microRNA-34a (miR-34a) binding its mRNA target, the silent information regulator 1 (mSIRT1), both with and without the Argonaute protein, constituting the RNA-induced silencing complex (RISC). We show that the seed of the mRNA target must be bound to the microRNA-loaded into RISC to enable further binding of the compensatory region by RISC, while the naked miR-34a is able to bind the compensatory region without seed interaction. The method presented here provides complementary structural evidence for the commonly performed luciferase-assay-based evaluation of microRNA binding-site efficiency and specificity on the mRNA target site and could therefore be used in conjunction with it. The method can be applied to any nucleic acid-mediated RNA- or RBP-binding process, such as splicing, antisense RNA binding, or regulation by RISC, providing important insight into the targeted RNA structure.

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Section: Resultssupporting

confidence: 75%

RNA:RNA interaction in ternary complexes resolved by chemical probing

Banijamali

Baronti

Becker

et al. 2022

RNA

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“…Two sets of MD simulations for this system were run. The Amber force field with revised χ and α/γ torsional parameters were used in both regular and umbrella sampling MD simulations, as these revised parameters have been shown to improve the predictions. ,,− …”

Section: Methodsmentioning

confidence: 99%

Computational Investigation of RNA CUG Repeats Responsible for Myotonic Dystrophy 1

Yildirim

Chakraborty

Disney

et al. 2015

J. Chem. Theory Comput.

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Myotonic Dystrophy 1 (DM1) is a genetic disease caused by expansion of CTG repeats in DNA. Once transcribed, these repeats form RNA hairpins with repeating 1×1 nucleotide UU internal loop motifs, r(CUG)n, which attract muscleblind-like 1 (MBNL1) protein leading to the disease. In DM1 CUG can be repeated thousands of times, so these structures are intractable to characterization using structural biology. However, inhibition of MBNL1-r(CUG)n binding requires a detailed analysis of the 1×1 UU internal loops. In this contribution we employ regular and umbrella sampling molecular dynamics (MD) simulations to describe the structural and thermodynamic properties of 1×1 UU internal loops. Calculations were run on a reported crystal structure and a designed system, which mimics an infinitely long RNA molecule with continuous CUG repeats. Two-dimensional (2D) potential of mean force (PMF) surfaces were created by umbrella sampling, and the discrete path sampling (DPS) method was utilized to investigate the energy landscape of 1×1 UU RNA internal loops, revealing that 1×1 UU base pairs are dynamic and strongly prefer the anti–anti conformation. Two 2D PMF surfaces were calculated for the 1×1 UU base pairs, revealing several local minima and three syn–anti ↔ anti–anti transformation pathways. Although at room temperature the syn–anti ↔ anti–anti transformation is not observed on the MD time scale, one of these pathways dominates the dynamics of the 1×1 UU base pairs in temperature jump MD simulations. This mechanism has now been treated successfully using the DPS approach. Our results suggest that local minima predicted by umbrella sampling calculations could be stabilized by small molecules, which is of great interest for future drug design. Furthermore, distorted GC/CG conformations may be important in understanding how MBNL1 binds to RNA CUG repeats. Hence we provide new insight into the dynamic roles of RNA loops and their contributions to presently incurable diseases.

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Improvement of RNA Simulations with Torsional Revisions of the AMBER Force Field

Yildirim

2019

Methods in Molecular Biology

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Correction to NMR of CCCC RNA Reveals a Right-Handed Helix and Revised Parameters for AMBER Force Field Torsions Improve Structural Predictions from Molecular Dynamics

Cited by 3 publications

References 0 publications

RNA:RNA interaction in ternary complexes resolved by chemical probing

RNA:RNA interaction in ternary complexes resolved by chemical probing

Computational Investigation of RNA CUG Repeats Responsible for Myotonic Dystrophy 1

Improvement of RNA Simulations with Torsional Revisions of the AMBER Force Field

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