A new way to see RNA

Keating, Kevin S.; Humphris, Elisabeth L.; Pyle, Anna Marie

doi:10.1017/s0033583511000059

Cited by 29 publications

(26 citation statements)

References 111 publications

(297 reference statements)

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“…To characterize structural differences between D1 iso and D1 full , we adapted an alternative computational method that has been successfully employed to identify specific motifs within RNA structures, to quantitatively analyze conformational changes upon ligand binding, and to model RNA into electron density 25 – 27 . This approach takes advantage of the fact that local and global RNA structure can be accurately reflected by a string of angular coordinates (called η and θ) that are analogous to dihedral angles φ and ψ in protein structures ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…This approach takes advantage of the fact that local and global RNA structure can be accurately reflected by a string of angular coordinates (called η and θ) that are analogous to dihedral angles φ and ψ in protein structures ( Fig. 4a ) 25 . In RNA, the η and θ angles (which describe the angular position of vectors connecting sequential P and C4′ atoms of the RNA backbone) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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Crystal structure of group II intron domain 1 reveals a template for RNA assembly

et al. 2015

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Although the importance of large noncoding RNAs is increasingly appreciated, our understanding of their structures and architectural dynamics remains limited. In particular, we know little about RNA folding intermediates and how they facilitate the productive assembly of RNA tertiary structures. Here, we report the crystal structure of an obligate intermediate that is required during the earliest stages of group II intron folding. Comprised of intron domain 1 from the Oceanobacillus iheyensis group II intron (D1, 266 nts), this intermediate retains native-like features but adopts a compact conformation in which the active-site cleft is closed. Transition between this closed and open (native) conformation is achieved through discrete rotations of hinge motifs in two regions of the molecule. The open state is then stabilized by sequential docking of downstream intron domains, suggesting a “first comes, first folds” strategy that may represent a generalizable pathway for assembly of large RNA and ribonucleoprotein structures.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Crystal structure of group II intron domain 1 reveals a template for RNA assembly

et al. 2015

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“…RNA secondary and tertiary structures [16,17] including hybrid DNA/RNA and quadruplex RNA (qRNA), have been less extensively studied by ESI-MS. This is perhaps surprising given the important roles of RNA at all stages of expression of the genome (DNA) from DNA replication through transcription to gene silencing.…”

Section: Introductionmentioning

confidence: 99%

ESI-MS Investigation of an Equilibrium between a Bimolecular Quadruplex DNA and a Duplex DNA/RNA Hybrid

Birrento

Bryan

Samosorn

et al. 2015

J. Am. Soc. Mass Spectrom.

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, J. L. (2015). ESI-MS investigation of an equilibrium between a bimolecular quadruplex DNA and a duplex DNA/RNA hybrid. Journal of the American Society for Mass Spectrometry, 26 (7), 1165-1173.ESI-MS investigation of an equilibrium between a bimolecular quadruplex DNA and a duplex DNA/RNA hybrid AbstractElectrospray ionization mass spectrometry (ESI-MS) conditions were optimized for simultaneous observation of a bimolecular qDNA and a Watson-Crick base-paired duplex DNA/RNA hybrid. The DNA sequence used was telomeric DNA, and the RNA contained the template for telomerase-mediated telomeric DNA synthesis. Addition of RNA to the quadruplex DNA (qDNA) resulted in formation of the duplex DNA/ RNA hybrid. Melting profiles obtained using circular dichroism spectroscopy confirmed that the DNA/RNA hybrid exhibited greater thermal stability than the bimolecular qDNA in solution. Binding of a 13-substituted berberine (1) derivative to the bimolecular qDNA stabilized its structure as evidenced by an increase in its stability in the mass spectrometer, and an increase in its circular dichroism (CD) melting temperature of 10°C. The DNA/RNA hybrid did not bind the ligand extensively and its thermal stability was unchanged in the presence of (1). The qDNA-ligand complex resisted unfolding in the presence of excess RNA, limiting the formation of the DNA/RNA hybrid. Previously, it has been proposed that DNA secondary structures, such as qDNA, may be involved in the telomerase mechanism. DNA/RNA hybrid structures occur at the active site of telomerase. The results presented in the current work show that if telomeric DNA was folded into a qDNA structure, it is possible for a DNA/RNA hybrid to form as is required during template alignment. The discrimination of ligand (1) AbstractElectrospray ionization mass spectrometry (ESI-MS) conditions were optimized for simultaneous observation of a bimolecular qDNA and a Watson-Crick base-paired duplex DNA/RNA hybrid. The DNA sequence used was telomeric DNA, and the RNA contained the template for telomerase-mediated telomeric DNA synthesis. Addition of RNA to the qDNA resulted in formation of the duplex DNA/RNA hybrid. Melting profiles obtained using circular dichroism spectroscopy confirmed that the DNA/RNA hybrid exhibited greater thermal stability than the bimolecular qDNA in solution. Binding of a 13-substituted berberine (1) derivative to the bimolecular qDNA stabilized its structure as evidenced by an increase in its stability in the mass spectrometer, and an increase in its (CD) melting temperature of 10 C. The DNA/RNA hybrid did not bind the ligand extensively and its thermal stability was unchanged in the presence of (1). The qDNA-ligand complex resisted unfolding in the presence of excess RNA, limiting the formation of the DNA/RNA hybrid.Previously, it has been proposed that DNA secondary structures, such as qDNA, may be involved in the telomerase mechanism. DNA/RNA hybrid structures occur at the active site of telomerase. The results presented in the current work show that if tel...

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“…Three way junctions[70, 72] with tertiary contacts[27] - the L1L fold - are recurrent and versatile folds for RNA function and the characterization of L1L dynamics in solution can help us understand their important role in RNA dynamics. The use of virtual torsions to distinguish between different folds is “a new way to see RNA” [64]. We show here and elsewhere[48] that virtual torsions can be used to distinguish between L1L conformations in the crystal as well as in solution.…”

Section: Resultsmentioning

confidence: 75%

Mapping L1 Ligase Ribozyme Conformational Switch

Giambaşu

Scott

et al. 2012

Journal of Molecular Biology

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L1 Ligase (L1L)molecular switch is an in vitro optimized synthetic allosteric ribozyme that catalyzes the regioselective formation of a 5’-to-3’ phosphodiester bond, a reaction for which there is no known naturally occurring RNA catalyst. L1L serves as a proof of principle that RNA can catalyze a critical reaction for prebiotic RNA self-replication according to the RNA World hypothesis. L1L crystal structure captures two distinct conformations that differ by a re-orientation of one of the stems by around 80 Å and are presumed to correspond to the active and inactive state, respectively. It is of great interest to understand the nature of these two states in solution, and the pathway for their interconversion. In this study, we use explicit solvent molecular simulation together with a novel enhanced sampling method that utilizes concepts from network theory to map out the conformational transition between active and inactive states of L1L. We find that the overall switching mechanism can be described as a 3-state/2-step process. The first step involves a large-amplitude swing that re-orients stem C. The second step involves the allosteric activation of the catalytic site through distant contacts with stem C. Using a conformational space network representation of the L1L switch transition, it is shown that the connection between the three states follows different topographical patterns: the stem C swing step passes through a narrow region of the conformational space network, whereas the allosteric activation step covers a much wider region and a more diverse set of pathways through the network.

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A new way to see RNA

Cited by 29 publications

References 111 publications

Crystal structure of group II intron domain 1 reveals a template for RNA assembly

Crystal structure of group II intron domain 1 reveals a template for RNA assembly

ESI-MS Investigation of an Equilibrium between a Bimolecular Quadruplex DNA and a Duplex DNA/RNA Hybrid

Mapping L1 Ligase Ribozyme Conformational Switch

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