Local cation-clamping distorts and softens RNA duplex

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.