Temperature-dependent twist of double-stranded RNA probed by magnetic tweezer experiments and molecular dynamics simulations

  • 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 withRNA 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.show moreshow less

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Metadaten
Author:Hana Dohnalová, Mona Seifert, Eva Matoušková, Misha Klein, Flávia S. Papini, Jan LipfertORCiDGND, David Dulin, Filip Lankaš
URN:urn:nbn:de:bvb:384-opus4-1142059
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/114205
ISSN:1520-6106OPAC
ISSN:1520-5207OPAC
Parent Title (English):The Journal of Physical Chemistry B
Publisher:American Chemical Society (ACS)
Type:Article
Language:English
Year of first Publication:2024
Publishing Institution:Universität Augsburg
Release Date:2024/07/22
Volume:128
Issue:3
First Page:664
Last Page:675
DOI:https://doi.org/10.1021/acs.jpcb.3c06280
Institutes:Mathematisch-Naturwissenschaftlich-Technische Fakultät
Mathematisch-Naturwissenschaftlich-Technische Fakultät / Institut für Physik
Mathematisch-Naturwissenschaftlich-Technische Fakultät / Institut für Physik / Lehrstuhl für Experimentalphysik I
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 53 Physik / 530 Physik
Licence (German):License LogoCC-BY 4.0: Creative Commons: Namensnennung (mit Print on Demand)