Local cation-clamping distorts and softens RNA duplex

Chen Zhang; Hai-Long Dong; Jia-Hao Zhang; Liang Dai; Yan Zhang; Zhi-Jie Tan; Xing-Hua Zhang

doi:10.1038/s42003-026-09580-4

Local cation-clamping distorts and softens RNA duplex

Chen Zhang (Co-first Author)
, Hai-Long Dong (Co-first Author)
, Jia-Hao Zhang
, Liang Dai
, Yan Zhang^*
, Zhi-Jie Tan^*
, Xing-Hua Zhang^*

^*Corresponding author for this work

Department of Physics

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

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Abstract

Multivalent cations are essential for DNA and RNA structures and their functions. However, how multivalent cations and their accompanying anions jointly reshape nucleic-acid mechanics, and why DNA and RNA respond so differently, remain unclear. Here we show using single-molecule magnetic tweezers that increasing multivalent cation concentrations first softens and then stiffens DNA due to charge inversion, whereas RNA first stiffens and then softens by over twofold. Our all-atom simulations reproduce these effects and reveal a physical mechanism: at low concentrations, multivalent cations clamp the RNA major groove, stiffening RNA; at higher concentrations, anions disrupt this groove clamping and promote local cation-clamping that distorts and softens RNA. The mechanism also explains changes in stretching modulus, contour length, and twist-stretch coupling. Our findings reveal that local cation-clamping sharply softens RNA and highlight the significant roles of anions in modulating RNA structure, providing a framework for tuning nucleic-acid mechanics in vitro for RNA-related applications. © The Author(s) 2026.

Original language	English
Article number	308
Number of pages	9
Journal	Communications Biology
Volume	9
Online published	23 Jan 2026
DOIs	https://doi.org/10.1038/s42003-026-09580-4
Publication status	Published - 2026

Funding

We are grateful to financial support from the National Natural Science Foundation of China (No. 12374216 and 12074294 to X.-H.Z.; No. 12375038 and 12075171 to Z.-J. T; No. 12304254 to C.Z; No. 22273080 to L.D), Hubei Provincial Natural Science Foundation of China (No. 2024AFE008 and 2025AFA021 to X.-H.Z.), Super Computing Center of Wuhan University, and the National Supercomputer Center in Guangzhou.

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This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/

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abstract = "Multivalent cations are essential for DNA and RNA structures and their functions. However, how multivalent cations and their accompanying anions jointly reshape nucleic-acid mechanics, and why DNA and RNA respond so differently, remain unclear. Here we show using single-molecule magnetic tweezers that increasing multivalent cation concentrations first softens and then stiffens DNA due to charge inversion, whereas RNA first stiffens and then softens by over twofold. Our all-atom simulations reproduce these effects and reveal a physical mechanism: at low concentrations, multivalent cations clamp the RNA major groove, stiffening RNA; at higher concentrations, anions disrupt this groove clamping and promote local cation-clamping that distorts and softens RNA. The mechanism also explains changes in stretching modulus, contour length, and twist-stretch coupling. Our findings reveal that local cation-clamping sharply softens RNA and highlight the significant roles of anions in modulating RNA structure, providing a framework for tuning nucleic-acid mechanics in vitro for RNA-related applications. {\textcopyright} The Author(s) 2026.",

author = "Chen Zhang and Hai-Long Dong and Jia-Hao Zhang and Liang Dai and Yan Zhang and Zhi-Jie Tan and Xing-Hua Zhang",

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T1 - Local cation-clamping distorts and softens RNA duplex

AU - Zhang, Chen

AU - Dong, Hai-Long

AU - Zhang, Jia-Hao

AU - Dai, Liang

AU - Zhang, Yan

AU - Tan, Zhi-Jie

AU - Zhang, Xing-Hua

PY - 2026

Y1 - 2026

N2 - Multivalent cations are essential for DNA and RNA structures and their functions. However, how multivalent cations and their accompanying anions jointly reshape nucleic-acid mechanics, and why DNA and RNA respond so differently, remain unclear. Here we show using single-molecule magnetic tweezers that increasing multivalent cation concentrations first softens and then stiffens DNA due to charge inversion, whereas RNA first stiffens and then softens by over twofold. Our all-atom simulations reproduce these effects and reveal a physical mechanism: at low concentrations, multivalent cations clamp the RNA major groove, stiffening RNA; at higher concentrations, anions disrupt this groove clamping and promote local cation-clamping that distorts and softens RNA. The mechanism also explains changes in stretching modulus, contour length, and twist-stretch coupling. Our findings reveal that local cation-clamping sharply softens RNA and highlight the significant roles of anions in modulating RNA structure, providing a framework for tuning nucleic-acid mechanics in vitro for RNA-related applications. © The Author(s) 2026.

AB - Multivalent cations are essential for DNA and RNA structures and their functions. However, how multivalent cations and their accompanying anions jointly reshape nucleic-acid mechanics, and why DNA and RNA respond so differently, remain unclear. Here we show using single-molecule magnetic tweezers that increasing multivalent cation concentrations first softens and then stiffens DNA due to charge inversion, whereas RNA first stiffens and then softens by over twofold. Our all-atom simulations reproduce these effects and reveal a physical mechanism: at low concentrations, multivalent cations clamp the RNA major groove, stiffening RNA; at higher concentrations, anions disrupt this groove clamping and promote local cation-clamping that distorts and softens RNA. The mechanism also explains changes in stretching modulus, contour length, and twist-stretch coupling. Our findings reveal that local cation-clamping sharply softens RNA and highlight the significant roles of anions in modulating RNA structure, providing a framework for tuning nucleic-acid mechanics in vitro for RNA-related applications. © The Author(s) 2026.

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DO - 10.1038/s42003-026-09580-4

M3 - RGC 21 - Publication in refereed journal

SN - 2399-3642

VL - 9

JO - Communications Biology

JF - Communications Biology

M1 - 308

ER -

Local cation-clamping distorts and softens RNA duplex

Abstract

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