Hidden intermediates in Mango III RNA aptamer folding revealed by pressure perturbation

Harish, Balasubramanian; Wang, Jinqiu; Hayden, Eric J.; Grabe, Bastian; Hiller, Wolf; Winter, Roland; Royer, Catherine A.

doi:10.1016/j.bpj.2021.12.037

Cited by 8 publications

(7 citation statements)

References 58 publications

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“…Recently it was found that noncanonical nucleic acid structure, such as DNA hairpins (DNA-HP), i-motifs, and G-quadruplexes (G4Qs), are much more pressure sensitive, and their pressure sensitivity varies with their base sequence and the type and concentration of the counterions present in solution. − Guanine-rich nucleic acid molecules are able to fold into a G-quadruplex. Structurally, G4Qs are stabilized by stacked G-tetrads and centrally coordinated cations (Na + or K + ).…”

Section: Resultsmentioning

confidence: 99%

Life in Multi-Extreme Environments: Brines, Osmotic and Hydrostatic Pressure─A Physicochemical View

et al. 2022

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Elucidating the details of the formation, stability, interactions, and reactivity of biomolecular systems under extreme environmental conditions, including high salt concentrations in brines and high osmotic and high hydrostatic pressures, is of fundamental biological, astrobiological, and biotechnological importance. Bacteria and archaea are able to survive in the deep ocean or subsurface of Earth, where pressures of up to 1 kbar are reached. The deep subsurface of Mars may host high concentrations of ions in brines, such as perchlorates, but we know little about how these conditions and the resulting osmotic stress conditions would affect the habitability of such environments for cellular life. We discuss the combined effects of osmotic (salts, organic cosolvents) and hydrostatic pressures on the structure, stability, and reactivity of biomolecular systems, including membranes, proteins, and nucleic acids. To this end, a variety of biophysical techniques have been applied, including calorimetry, UV/vis, FTIR and fluorescence spectroscopy, and neutron and X-ray scattering, in conjunction with high pressure techniques. Knowledge of these effects is essential to our understanding of life exposed to such harsh conditions, and of the physical limits of life in general. Finally, we discuss strategies that not only help us understand the adaptive mechanisms of organisms that thrive in such harsh geological settings but could also have important ramifications in biotechnological and pharmaceutical applications.

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Section: Resultsmentioning

confidence: 99%

Life in Multi-Extreme Environments: Brines, Osmotic and Hydrostatic Pressure─A Physicochemical View

et al. 2022

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“…These studies were complemented with a detailed assessment of the effect of carbonecarbon coupling on relaxation parameters measured in samples with different labeling schemes [62] and with quantification of the effect of 13 C dipolar coupling on relaxation rates, which become non-negligible, especially at the higher magnetic field and large molecular weights of RNAs [63]. The high-pressure NMR was also shown to be useful for the detection of low-abundance excited states of RNA [64].…”

Section: Methodological Developmentsmentioning

confidence: 99%

NMR of RNA - Structure and interactions

Marušič

Toplishek

Plavec

2023

Current Opinion in Structural Biology

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“…A study by the Royer lab showed that pressure can be used to probe the structural excited states of the Mango III aptamer using both HHP fluorescence and NMR spectroscopy approaches. 95 Depending on the KCl concentration, parallel folding and/or binding pathways could be revealed, demonstrating the usefulness of pressure for characterizing also RNA folding intermediates. Further, as microbes commonly use RNA structural changes to regulate gene expression (i.e., riboswitches), it is conceivable that pressure-induced RNA structural changes could also be used to modulate homeostasis in high-pressure organisms.…”

Section: Volume-sensitive Conformational Changes Phase Transitions An...mentioning

confidence: 97%

“…Fluorescent RNA aptamers have the potential to enable routine quantitation and localization of RNA molecules and to serve as models for understanding biologically active aptamers. A study by the Royer lab showed that pressure can be used to probe the structural excited states of the Mango III aptamer using both HHP fluorescence and NMR spectroscopy approaches . Depending on the KCl concentration, parallel folding and/or binding pathways could be revealed, demonstrating the usefulness of pressure for characterizing also RNA folding intermediates.…”

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confidence: 99%

Harnessing Pressure-Axis Experiments to Explore Volume Fluctuations, Conformational Substates, and Solvation of Biomolecular Systems

Oliva

Winter

2022

J. Phys. Chem. Lett.

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Intrinsic thermodynamic fluctuations within biomolecules are crucial for their function, and flexibility is one of the strategies that evolution has developed to adapt to extreme environments. In this regard, pressure perturbation is an important tool for mechanistically exploring the causes and effects of volume fluctuations in biomolecules and biomolecular assemblies, their role in biomolecular interactions and reactions, and how they are affected by the solvent properties. High hydrostatic pressure is also a key parameter in the context of deep-sea and subsurface biology and the study of the origin and physical limits of life. We discuss the role of pressure-axis experiments in revealing intrinsic structural fluctuations as well as high-energy conformational substates of proteins and other biomolecular systems that are important for their function and provide some illustrative examples. We show that the structural and dynamic information obtained from such pressure-axis studies improves our understanding of biomolecular function, disease, biological evolution, and adaptation.

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Hidden intermediates in Mango III RNA aptamer folding revealed by pressure perturbation

Cited by 8 publications

References 58 publications

Life in Multi-Extreme Environments: Brines, Osmotic and Hydrostatic Pressure─A Physicochemical View

Life in Multi-Extreme Environments: Brines, Osmotic and Hydrostatic Pressure─A Physicochemical View

NMR of RNA - Structure and interactions

Harnessing Pressure-Axis Experiments to Explore Volume Fluctuations, Conformational Substates, and Solvation of Biomolecular Systems

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