Temperature-Dependent Twist of Double-Stranded RNA Probed by Magnetic Tweezer Experiments and Molecular Dynamics Simulations

Dohnalová H, Seifert M, Matoušková E, Klein M, Stal Papini F, Lipfert J, Dulin D, Lankaš F (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Journal of Physical Chemistry B American Chemical Society

Book Volume: 128

Pages Range: 664-675

Journal Issue: 3

DOI: 10.1021/acs.jpcb.3c06280

Abstract

RNA plays critical roles in the transmission and regulation of genetic information and is increasingly used in biomedical and biotechnological applications. Functional RNAs contain extended double-stranded regions, and the structure of double-stranded RNA (dsRNA) has been revealed at high resolution. However, the dependence of the properties of the RNA double helix on environmental effects, notably temperature, is still poorly understood. Here, we use single-molecule magnetic tweezer measurements to determine the dependence of the dsRNA twist on temperature. We find that dsRNA unwinds with increasing temperature, even more than DNA, with ΔTwRNA = −14.4 ± 0.7°/(°C·kbp), compared to ΔTwDNA = −11.0 ± 1.2°/(°C·kbp). All-atom molecular dynamics (MD) simulations using a range of nucleic acid force fields, ion parameters, and water models correctly predict that dsRNA unwinds with rising temperature but significantly underestimate the magnitude of the effect. These MD data, together with additional MD simulations involving DNA and DNA-RNA hybrid duplexes, reveal a linear correlation between the twist temperature decrease and the helical rise, in line with DNA but at variance with RNA experimental data. We speculate that this discrepancy might be caused by some unknown bias in the RNA force fields tested or by as yet undiscovered transient alternative structures in the RNA duplex. Our results provide a baseline to model more complex RNA assemblies and to test and develop new parametrizations for RNA simulations. They may also inspire physical models of the temperature-dependent dsRNA structure.

Authors with CRIS profile

Mona Seifert Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 2 Prof. Dr. Dulin David Dulin Interdisziplinäres Zentrum für Klinische Forschung IZKF Nachwuchsgruppe 2 Prof. Dr. Dulin

Involved external institutions

University of Chemistry and Technology (UCT) / Vysoká škola chemicko-technologická (VŠCHT) CZ Czech Republic (CZ) Vrije Universiteit Amsterdam (VU) / University Amsterdam NL Netherlands (NL) Debye Institute for Nanomaterials Science NL Netherlands (NL)

How to cite

APA:

Dohnalová, H., Seifert, M., Matoušková, E., Klein, M., Stal Papini, F., Lipfert, J.,... Lankaš, F. (2024). Temperature-Dependent Twist of Double-Stranded RNA Probed by Magnetic Tweezer Experiments and Molecular Dynamics Simulations. Journal of Physical Chemistry B, 128(3), 664-675. https://doi.org/10.1021/acs.jpcb.3c06280

MLA:

Dohnalová, Hana, et al. "Temperature-Dependent Twist of Double-Stranded RNA Probed by Magnetic Tweezer Experiments and Molecular Dynamics Simulations." Journal of Physical Chemistry B 128.3 (2024): 664-675.

BibTeX: Download