These are the sources and citations used to research RNA dynamics. This bibliography was generated on Cite This For Me on
In-text: (Al-Hashimi 1506-1519)
Your Bibliography: Al-Hashimi, Hashim M. "Dynamics-Based Amplification Of RNA Function And Its Characterization By Using NMR Spectroscopy." ChemBioChem 6.9 (2005): 1506-1519. Web.
In-text: (Buck et al. 15699-15704)
Your Bibliography: Buck, J. et al. "Time-Resolved NMR Methods Resolving Ligand-Induced RNA Folding At Atomic Resolution." Proceedings of the National Academy of Sciences 104.40 (2007): 15699-15704. Web.
Transitions between different conformational states, so-called conformational switching, are intrinsic to RNA catalytic and regulatory functions. Often, conformational switching occurs on time scales of several seconds. In combination with the recent real-time NMR experiments (Wenter et al. Angew. Chem. Int. Ed. 2005, 44, 2600; Wenter et al. ChemBioChem 2006, 7, 417) for the transitions between bistable RNA conformations, we combine the master equation method with the kinetic cluster method to investigate the detailed kinetic mechanism and the factors that govern the folding kinetics. We propose that heat capacity change (ΔCp) upon RNA folding may be important for RNA folding kinetics. In addition, we find that, for tetraloop hairpins, noncanonical (tertiary) intraloop interactions are important to determine the folding kinetics. Furthermore, through theory-experiment comparisons, we find that the different rate models for the fundamental steps (i.e., formation/disruption of a base pair or stack) can cause contrasting results in the theoretical predictions
In-text: (Cao et al. 13609-13615)
Your Bibliography: Cao, Song et al. "Folding Kinetics For The Conformational Switch Between Alternative RNA Structures." The Journal of Physical Chemistry B 114.42 (2010): 13609-13615. Web.
Recent studies have shown that RNAs exist in dynamic equilibrium with short-lived low-abundance ‘excited states’ that form by reshuffling base pairs in and around non-canonical motifs. These conformational states are proposed to be rich in non-canonical motifs and to play roles in the folding and regulatory functions of non-coding RNAs but their structure proves difficult to characterize given their transient nature. Here, we describe an approach for determining sugar pucker conformation in RNA excited states through nuclear magnetic resonance measurements of C1΄ and C4΄ rotating frame spin relaxation (R1ρ) in uniformly 13C/15N labeled RNA samples. Application to HIV-1 TAR exposed slow modes of sugar repuckering dynamics at the μs and ms timescale accompanying transitions between non-helical (C2΄-endo) to helical (C3΄-endo) conformations during formation of two distinct excited states. In contrast, we did not obtain any evidence for slow sugar repuckering dynamics for nucleotides in a variety of structural contexts that do not undergo non-helical to helical transitions. Our results outline a route for significantly improving the conformational characterization of RNA excited states and suggest that slow modes of repuckering dynamics gated by transient changes in secondary structure are quite common in RNA.
In-text: (Clay et al. e134-e134)
Your Bibliography: Clay, Mary C. et al. "Resolving Sugar Puckers In RNA Excited States Exposes Slow Modes Of Repuckering Dynamics." Nucleic Acids Research 45 (2017): e134-e134. Web.
In-text: (Cruz and Westhof 604-609)
Your Bibliography: Cruz, José Almeida, and Eric Westhof. "The Dynamic Landscapes Of RNA Architecture." Cell 136 (2009): 604-609. Web.
Cited in connection with importance of NMR for nucleic acids
In-text: (Cruz and Westhof 604-609)
Your Bibliography: Cruz, José Almeida, and Eric Westhof. "The Dynamic Landscapes Of RNA Architecture." Cell 136.4 (2009): 604-609. Web.
Despite the large number of noncoding RNAs and their importance in several biological processes, our understanding of RNA structure and dynamics at atomic resolution is still very limited. Like many other RNAs, the Neurospora Varkud satellite (VS) ribozyme performs its functions through dynamic exchange of multiple conformational states. More specifically, the VS ribozyme recognizes and cleaves its stem-loop substrate via a mechanism that involves several structural transitions within its stem-loop substrate. The recent publications of high-resolution structures of the VS ribozyme, obtained by NMR spectroscopy and X-ray crystallography, offer an opportunity to integrate the data and closely examine the structural and dynamic properties of this model RNA system. Notably, these investigations provide a valuable example of the divide-and-conquer strategy for structural and dynamic characterization of a large RNA, based on NMR structures of several individual subdomains. The success of this divide-and-conquer approach reflects the modularity of RNA architecture and the great care taken in identifying the independently-folding modules. Together with previous biochemical and biophysical characterizations, the recent NMR and X-ray studies provide a coherent picture into how the VS ribozyme recognizes its stem-loop substrate. Such in-depth characterization of this RNA enzyme will serve as a model for future structural and engineering studies of dynamic RNAs and may be particularly useful in planning divide-and-conquer investigations. WIREs RNA 2017, 8:e1421. doi: 10.1002/wrna.1421 For further resources related to this article, please visit the WIREs website.
In-text: (Dagenais et al. e1421)
Your Bibliography: Dagenais, Pierre et al. "Insights Into RNA Structure And Dynamics From Recent NMR And X-Ray Studies Of The Neurospora Varkud Satellite Ribozyme." Wiley Interdisciplinary Reviews: RNA 8.5 (2017): e1421. Web.
In-text: (Dethoff et al. 322-330)
Your Bibliography: Dethoff, Elizabeth A. et al. "Functional Complexity And Regulation Through RNA Dynamics." Nature 482 (2012): 322-330. Web.
Many regulatory RNAs contain long single strands (ssRNA) that adjoin secondary structural elements. Here, we use NMR spectroscopy to study the dynamic properties of a 12-nucleotide (nt) ssRNA tail derived from the prequeuosine riboswitch linked to the 3' end of a 48-nt hairpin. Analysis of chemical shifts, NOE connectivity, (13)C spin relaxation, and residual dipolar coupling data suggests that the first two residues (A25 and U26) in the ssRNA tail stack onto the adjacent helix and assume an ordered conformation. The following U26-A27 step marks the beginning of an A6-tract and forms an acute pivot point for substantial motions within the tail, which increase toward the terminal end. Despite substantial internal motions, the ssRNA tail adopts, on average, an A-form helical conformation that is coaxial with the helix. Our results reveal a surprising degree of structural and dynamic complexity at the ssRNA-helix junction, which involves a fine balance between order and disorder that may facilitate efficient pseudoknot formation on ligand recognition.
In-text: (Eichhorn and Al-Hashimi 782-791)
Your Bibliography: Eichhorn, C. D., and H. M. Al-Hashimi. "Structural Dynamics Of A Single-Stranded RNA-Helix Junction Using NMR." RNA 20.6 (2014): 782-791. Web.
In-text: (Fürtig et al. 11.13.1-11.13.16)
Your Bibliography: Fürtig, Boris et al. "Characterization Of Conformational Dynamics Of Bistable RNA By Equilibrium And Non-Equilibrium NMR." Current Protocols in Nucleic Acid Chemistry 55.1 (2013): 11.13.1-11.13.16. Web.
The structural transition between two alternate conformations of bistable RNAs has been characterized by time-resolved NMR spectroscopy. The mechanism, kinetics, and thermodynamics underlying the global structural transition of bistable RNAs were delineated. Both bistable RNA conformations and a partial unstructured RNA of identical sequence could be trapped using photolabile protecting groups. This trapping allowed for an investigation of the initial folding from an unfolded RNA to one of the preferred conformations of the bistable RNA and of the structural transitions involved. Folding of the secondary structure elements occurs rapidly, while the global structural transition of the bistable RNA occurs on a time scale of minutes and shows marked temperature dependence. Comparison of these results with bistable systems previously investigated leads to the prediction of activation enthalpies (ΔH⧧) associated with global structural transitions in RNA.
In-text: (Fürtig et al. 16222-16229)
Your Bibliography: Fürtig, Boris et al. "Conformational Dynamics Of Bistable Rnas Studied By Time-Resolved NMR Spectroscopy." Journal of the American Chemical Society 129.51 (2007): 16222-16229. Web.
The application of real-time NMR experiments to the study of RNA folding, as reviewed in this article, is relatively new. For many RNA folding events, current investigations suggest that the time scales are in the second to minute regime. In addition, the initial investigations suggest that different folding rates are observed for one structural transition may be due to the hierarchical folding units of RNA. Many of the experiments developed in the field of NMR of protein folding cannot directly be transferred to RNA: hydrogen exchange experiments outside the spectrometer cannot be applied since the intrinsic exchange rates are too fast in RNA, relaxation dispersion experiments on the other require faster structural transitions than those observed in RNA. On the other hand, information derived from time-resolved NMR experiments, namely the acquisition of native chemical shifts, can be readily interpreted in light of formation of a single long-range hydrogen bonding interaction. Together with mutational data that can readily be obtained for RNA and new ligation technologies that enhance site resolution even further, time-resolved NMR may become a powerful tool to decipher RNA folding. Such understanding will be of importance to understand the functions of coding and non-coding RNAs in cells. # 2007 Wiley Periodicals, Inc. Biopolymers 86: 360–383, 2007. Keywords: NMR spectroscopy; RNA folding; time-resolved NMR; photolabile caged compounds
In-text: (Fürtig et al. 360-383)
Your Bibliography: Fürtig, Boris et al. "Time-Resolved NMR Studies Of RNA Folding." Biopolymers 86.5-6 (2007): 360-383. Web.
An increasing number of RNAs are being discovered that perform their functions by undergoing large changes in conformation in response to a variety of cellular signals, including recognition of proteins and small molecular targets, changes in temperature, and RNA synthesis itself. The measurement of NMR residual dipolar couplings (RDCs) in partially aligned systems is providing new insights into the structural plasticity of RNA through combined characterization of large-amplitude collective helix motions and local flexibility in noncanonical regions over a wide window of biologically relevant timescales (<milliseconds). Here, we review RDC methodology for studying RNA structural dynamics and survey what has been learnt thus far from application of these methods. Future methodological challenges are also identified.
In-text: (Getz et al. 384-402)
Your Bibliography: Getz, Melissa et al. "Review NMR Studies Of RNA Dynamics And Structural Plasticity Using NMR Residual Dipolar Couplings." Biopolymers 86.5-6 (2007): 384-402. Web.
In-text: (Lindén et al. 418a)
Your Bibliography: Lindén, Martin et al. "Analysis Of DNA Looping Kinetics In Tethered Particle Motion Experiments Using Hidden Markov Models." Biophysical Journal 104 (2013): 418a. Web.
Internal ribosome entry site (IRES) elements are RNA regions that recruit the translation machinery internally. Here we investigated the conformational changes and RNA dynamics of a picornavirus IRES upon incubation with distinct ribosomal fractions. Differential SHAPE analysis of the free RNA showed that nucleotides reaching the final conformation on long timescales were placed at domains 4 and 5, while candidates for long-range interactions were located in domain 3. Salt-washed ribosomes induced a fast RNA local flexibility modification of domains 2 and 3, while ribosome-associated factors changed. domains 4 and 5. Consistent with this, modeling of the three-dimensional RNA structure indicated that incubation of the IRES with native ribosomes induced a local rearrangement of the apical region of domain 3, and a reorientation of domains 4 and 5. Furthermore, specific motifs within domains 2 and 3 showed a decreased flexibility upon incubation with ribosomal subunits in vitro, and presence of the IRES enhanced mRNA association to the ribosomal subunits in whole cell lysates. The finding that RNA modules can provide direct IRES-ribosome interaction suggests that linking these motifs to additional sequences able to recruit trans-acting factors could be useful to design synthetic IRESs with novel activities.
In-text: (Lozano, Francisco-Velilla and Martinez-Salas)
Your Bibliography: Lozano, Gloria, Rosario Francisco-Velilla, and Encarnacion Martinez-Salas. "Ribosome-Dependent Conformational Flexibility Changes And RNA Dynamics Of IRES Domains Revealed By Differential SHAPE." Scientific Reports 8.1 (2018): n. pag. Web.
In-text: (Lu et al. 5042-5057)
Your Bibliography: Lu, Jia et al. "Dynamic Ensemble View Of The Conformational Landscape Of HIV-1 TAR RNA And Allosteric Recognition." Biochemistry 50.22 (2011): 5042-5057. Web.
An ever-increasing number of functional RNAs require a mechanistic understanding. RNA function relies on changes in its structure, so-called dynamics. To reveal dynamic processes and higher energy structures, new NMR methods have been developed to elucidate these dynamics in RNA with atomic resolution. In this Review, we provide an introduction to dynamics novices and an overview of methods that access most dynamic timescales, from picoseconds to hours. Examples are provided as well as insight into theory, data acquisition and analysis for these different methods. Using this broad spectrum of methodology, unprecedented detail and invisible structures have been obtained and are reviewed here. RNA, though often more complicated and therefore neglected, also provides a great system to study structural changes, as these RNA structural changes are more easily defined—Lego like—than in proteins, hence the numerous revelations of RNA excited states.
In-text: (Marušič, Schlagnitweit and Petzold 2683-2683)
Your Bibliography: Marušič, Maja, Judith Schlagnitweit, and Katja Petzold. "Front Cover: RNA Dynamics By NMR Spectroscopy (Chembiochem 21/2019)." ChemBioChem 20.21 (2019): 2683-2683. Web.
The highly conserved internal stem–loop (ISL) of U6 spliceosomal RNA is unwound for U4/U6 complex formation during spliceosome assembly and reformed upon U4 release during spliceosome activation. The U6 ISL is structurally similar to Domain 5 of group II self-splicing introns, and contains a dynamic bulge that coordinates a Mg++ ion essential for the first catalytic step of splicing. We have analyzed the causes of growth defects resulting from mutations in the Saccharomyces cerevisiae U6 ISL-bulged nucleotide U80 and the adjacent C67–A79 base pair. Intragenic suppressors and enhancers of the cold-sensitive A79G mutation, which replaces the C–A pair with a C–G pair, suggest that it stabilizes the ISL, inhibits U4/U6 assembly, and may also disrupt spliceosome activation. The lethality of mutations C67A and C67G results from disruption of base-pairing potential between U4 and U6, as these mutations are fully suppressed by compensatory mutations in U4 RNA. Strikingly, suppressor analysis shows that the lethality of the U80G mutation is due not only to formation of a stable base pair with C67, as previously proposed, but also another defect. A U6-U80G strain in which mispairing with position 67 is prevented grows poorly and assembles aberrant spliceosomes that retain U1 snRNP and fail to fully unwind the U4/U6 complex at elevated temperatures. Our data suggest that the U6 ISL bulge is important for coupling U1 snRNP release with U4/U6 unwinding during spliceosome activation.
In-text: (McManus et al. 2252-2265)
Your Bibliography: McManus, C. J. et al. "A Dynamic Bulge In The U6 RNA Internal Stem Loop Functions In Spliceosome Assembly And Activation." RNA 13.12 (2007): 2252-2265. Web.
The HIV-1 frameshift site (FS) plays a critical role in viral replication. During translation, the HIV-1 FS transitions from a 3-helix to a 2-helix junction RNA secondary structure. The 2-helix junction structure contains a GGA bulge, and purine-rich bulges are common motifs in RNA secondary structure. Here, we investigate the dynamics of the HIV-1 FS 2-helix junction RNA. Interhelical motions were studied under different ionic conditions using NMR order tensor analysis of residual dipolar couplings. In 150 mM potassium, the RNA adopts a 43°(±4°) interhelical bend angle (β) and displays large amplitude, anisotropic interhelical motions characterized by a 0.52(±0.04) internal generalized degree of order (GDOint) and distinct order tensor asymmetries for its two helices (η = 0.26(±0.04) and 0.5(±0.1)). These motions are effectively quenched by addition of 2 mM magnesium (GDOint = 0.87(±0.06)), which promotes a near-coaxial conformation (β = 15°(±6°)) of the two helices. Base stacking in the bulge was investigated using the fluorescent purine analog 2-aminopurine. These results indicate that magnesium stabilizes extrahelical conformations of the bulge nucleotides, thereby promoting coaxial stacking of helices. These results are highly similar to previous studies of the HIV transactivation response RNA, despite a complete lack of sequence similarity between the two RNAs. Thus, the conformational space of these RNAs is largely determined by the topology of their interhelical junctions.
In-text: (Mouzakis et al. 644-654)
Your Bibliography: Mouzakis, Kathryn D. et al. "Dynamic Motions Of The HIV-1 Frameshift Site RNA." Biophysical Journal 108 (2015): 644-654. Web.
In-text: (Mustoe, Brooks and Al-Hashimi 441-466)
Your Bibliography: Mustoe, Anthony M., Charles L. Brooks, and Hashim M. Al-Hashimi. "Hierarchy Of RNA Functional Dynamics." Annual Review of Biochemistry 83 (2014): 441-466. Web.
In-text: (Plumridge et al. 433a)
Your Bibliography: Plumridge, Alex et al. "Time-Resolved SAXS And Ensemble Modelling Reveal Magnesium Orchestration Across An RNA Folding Landscape." Biophysical Journal 114.3 (2018): 433a. Web.
In-text: (Rinnenthal et al. 1292-1301)
Your Bibliography: Rinnenthal, Jörg et al. "Mapping The Landscape Of RNA Dynamics With NMR Spectroscopy." Accounts of Chemical Research 44.12 (2011): 1292-1301. Web.
Conformational changes in nucleic acids play a key role in the way genetic information is stored, transferred, and processed in living cells. Here, we describe new approaches that employ a broad range of experimental data, including NMR-derived chemical shifts and residual dipolar couplings, small-angle X-ray scattering, and computational approaches such as molecular dynamics simulations to determine ensembles of DNA and RNA at atomic resolution. We review the complementary information that can be obtained from diverse sets of data and the various methods that have been developed to combine these data with computational methods to construct ensembles and assess their uncertainty. We conclude by surveying RNA and DNA ensembles determined using these methods, highlighting the unique physical and functional insights obtained so far.
In-text: (Salmon, Yang and Al-Hashimi 293-316)
Your Bibliography: Salmon, Loïc, Shan Yang, and Hashim M. Al-Hashimi. "Advances In The Determination Of Nucleic Acid Conformational Ensembles." Annual Review of Physical Chemistry 65 (2014): 293-316. Web.
Clustered regularly interspaced short palindromic repeat (CRISPR) chromosomal loci found in prokaryotes provide an adaptive immune system against bacteriophages and plasmids. CRISPR-specific endoRNases produce short RNA molecules (crRNAs) from CRISPR transcripts, which harbor sequences complementary to invasive nucleic acid elements and ensure their selective targeting by CRISPR-associated (Cas) proteins. The extreme sequence divergence of CRISPR-specific endoRNases and their RNA substrates has obscured homology-based comparison of RNA recognition and cleavage mechanisms. Here, we show that Cse3 type CRISPRspecific endoRNases bind a hairpin structure and residues downstream of the cleavage site within the repetitive segment of cognate CRISPR RNA. Cocrystal structures of Cse3–RNA complexes reveal an RNA-induced conformational change in the enzyme active site that aligns the RNA strand for site-specific cleavage. These studies provide insight into a catalytically essential RNA recognition mechanism by a large class of CRISPR-related endoRNases
In-text: (Sashital, Jinek and Doudna 680-687)
Your Bibliography: Sashital, Dipali G, Martin Jinek, and Jennifer A Doudna. "An RNA-Induced Conformational Change Required For CRISPR RNA Cleavage By The Endoribonuclease Cse3." Nature Structural & Molecular Biology 18.6 (2011): 680-687. Web.
In-text: (Sattler 727-728)
Your Bibliography: Sattler, Michael. "Dynamic RNA World." RNA 21.4 (2015): 727-728. Web.
The dynamics of two DNA hairpins (5′-TCGCCT-A31-AGGCGA-3′ and 5′-TCGCCG-A31-CGGCGA-3′) were studied using immobilization-based and diffusion-based single-molecule fluorescence techniques. The techniques enabled separated and detailed investigation of the states and of the transition reactions. Only two states, open and closed, were identified from analysis of the FRET histograms; metastable states with lifetimes longer than the technique resolution (0.3 ms) were not observed. The opening and closing reaction rates were determined directly from the FRET time trajectories, and the Gibbs free energies of these states and of the transition state were calculated using the Kramer theory. The rates, which are undoubtedly of transitions between the fully closed and the fully open states and ranged from 2 to 90 s–1, were lower (∼10-fold) than the rates previously determined from fluorescence correlation spectroscopy. The heights of the barriers for closing were almost identical for the two hairpins. The barrier for opening the hairpin with the stronger stem was higher (4.3 kJ/mol) than that for the hairpin with the weaker stem, in very good agreement with the difference in stability calculated by the nearest-neighbor method. The barrier for closing the hairpin decreased (∼8 kJ/mol) and the barrier for opening increased (∼4 kJ/mol) with increasing NaCl concentration (10–100 mM), indicating that higher ionic strength stabilizes the folded state with respect to the transition state and stabilizes the transition state relative to the unfolded state. The very good agreements in the dynamics measured for free hairpins, for hairpins anchored to origami, and for hairpins anchored to the coverslip and the very good agreement between the two single-molecule techniques demonstrate that neither the origami nor the coverslip influence the hairpin dynamics, supporting a previous demonstration that origami can serve as a platform for biophysical investigations
In-text: (Tsukanov et al. 11932-11942)
Your Bibliography: Tsukanov, Roman et al. "Detailed Study Of DNA Hairpin Dynamics Using Single-Molecule Fluorescence Assisted By DNA Origami." The Journal of Physical Chemistry B 117.40 (2013): 11932-11942. Web.
In common with other self-cleaving RNAs, the lead-dependent ribozyme (leadzyme) undergoes dynamic fluctuations to a chemically activated conformation. We explored the connection between conformational dynamics and self-cleavage function in the leadzyme using a combination of NMR spin-relaxation analysis of ribose groups and conformational restriction via chemical modification. The functional studies were performed with a Northmethanocarbacytidine modification that prevents fluctuations to C2´-endo conformations while maintaining an intact 2´-hydroxyl nucleophile. Spin-relaxation data demonstrate that the activesite Cyt-6 undergoes conformational exchange attributed to sampling of a minor C2´-endo state with an exchange lifetime on the order of microseconds to tens of microseconds. A conformationally-restricted species in which the fluctuations to the minor species are interrupted shows a drastic decrease in self-cleavage activity. Taken together, these data indicate that dynamic sampling of a minor species at the active site of this ribozyme, and likely of related naturally-occurring motifs, is strongly coupled to catalytic function. The combination of NMR dynamics analysis with functional probing via conformational restriction is a general methodology for dissecting dynamics-function relationships in RNA.
In-text: (White et al. 1542-1554)
Your Bibliography: White, Neil A. et al. "Coupling Between Conformational Dynamics And Catalytic Function At The Active Site Of The Lead-Dependent Ribozyme." RNA 24.11 (2018): 1542-1554. Web.
In-text: (Zhang and Al-Hashimi 1941-1948)
Your Bibliography: Zhang, Q., and H. M. Al-Hashimi. "Domain-Elongation NMR Spectroscopy Yields New Insights Into RNA Dynamics And Adaptive Recognition." RNA 15.11 (2009): 1941-1948. Web.
In-text: (Zhang, Faraggi and Zhou 3353-3362)
Your Bibliography: Zhang, Tuo, Eshel Faraggi, and Yaoqi Zhou. "Fluctuations Of Backbone Torsion Angles Obtained From NMR-Determined Structures And Their Prediction." Proteins: Structure, Function, and Bioinformatics 78 (2010): 3353-3362. Web.
While the major architectural features and active-site components of group II introns have been known for almost a decade, information on the individual stages of splicing has been lacking. Recent advances in crystallography and cryo-electron microscopy (cryo-EM) have provided major new insights into the structure of intact lariat introns. Conformational changes that mediate the steps of splicing and retrotransposition are being elucidated, revealing the dynamic, highly coordinated motions that are required for group II intron activity. Finally, these ribozymes can now be viewed in their larger, more natural context as components of holoenzymes that include encoded maturase proteins. These studies expand our understanding of group II intron structural diversity and evolution, while setting the stage for rigorous mechanistic analysis of RNA splicing machines
In-text: (Zhao and Pyle 470-482)
Your Bibliography: Zhao, Chen, and Anna Marie Pyle. "Structural Insights Into The Mechanism Of Group II Intron Splicing." Trends in Biochemical Sciences 42.6 (2017): 470-482. Web.
In-text: (Zhao and Xia 128-135)
Your Bibliography: Zhao, Liang, and Tianbing Xia. "Probing RNA Conformational Dynamics And Heterogeneity Using Femtosecond Time-Resolved Fluorescence Spectroscopy." Methods 49.2 (2009): 128-135. Web.
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