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Chen Zhang1,2, Hai-Long Dong1,3, Jia-Hao Zhang1

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Multivalent cations and anions significantly alter DNA and RNA mechanics. Cations stiffen RNA at low concentrations but soften it at higher levels by disrupting major groove clamping.

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Biochemistry

Background:

  • Multivalent cations are crucial for DNA and RNA structure and function.
  • The combined effects of cations and anions on nucleic acid mechanics, and the differential responses of DNA and RNA, are not well understood.

Purpose of the Study:

  • To investigate how multivalent cations and anions jointly influence DNA and RNA mechanics.
  • To elucidate the distinct mechanical responses of DNA and RNA to varying cation concentrations.

Main Methods:

  • Single-molecule magnetic tweezers experiments were employed to measure DNA and RNA mechanics.
  • All-atom simulations were performed to reproduce experimental findings and reveal underlying physical mechanisms.

Main Results:

  • DNA mechanics showed softening followed by stiffening with increasing multivalent cation concentrations due to charge inversion.
  • RNA exhibited an initial stiffening, followed by a twofold softening at higher cation concentrations.
  • Simulations revealed that cations initially stiffen RNA by clamping the major groove, while anions at higher concentrations disrupt this and induce local clamping, leading to softening.

Conclusions:

  • The study reveals a novel mechanism for RNA softening driven by anion-mediated local cation-clamping.
  • Anions play a critical role in modulating RNA structure and mechanics.
  • Findings provide a framework for manipulating nucleic acid mechanics in vitro for RNA-based applications.