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Why double-stranded RNA resists condensation.

Igor S Tolokh1, Suzette A Pabit2, Andrea M Katz2

  • 1Department of Computer Science, Virginia Tech, Blacksburg, VA 24061, USA.

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|August 16, 2014
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Summary
This summary is machine-generated.

Multivalent cations like cobalt hexammine (CoHex) condense double-stranded DNA but not RNA. Condensation depends on how CoHex binds externally to nucleic acids (NA), not just their helical form.

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Computational Chemistry

Background:

  • Multivalent cations induce condensation of double-stranded deoxyribonucleic acid (DNA).
  • This condensation is unexpectedly suppressed in double-stranded ribonucleic acid (RNA), despite similar negative charge.
  • Differences in nucleic acid condensation are not fully explained by helical geometry alone.

Purpose of the Study:

  • To elucidate the mechanism behind differential condensation of various nucleic acid (NA) duplexes (DNA, RNA, DNA:RNA hybrids).
  • To investigate the role of cobalt hexammine (CoHex) binding in NA condensation.
  • To correlate NA condensation propensity with ion binding modes.

Main Methods:

  • Atomistic simulations were employed to model short (25 base-pair) nucleic acid duplexes.
  • Circular dichroism spectroscopy was used to analyze NA structures.
  • Cobalt hexammine (CoHex) binding interactions with different NA constructs were quantified.

Main Results:

  • Nucleic acid condensation is governed by the spatial distribution of CoHex binding, not solely helical geometry.
  • Two primary CoHex binding modes were identified: internal and external.
  • A significant variation (up to 5-fold) in the fraction of externally bound CoHex was observed across different NA duplexes.

Conclusions:

  • The propensity of nucleic acids to condense is determined by the fraction of CoHex ions bound to their external surfaces.
  • External ion binding, influenced by NA structure, is the key factor regulating condensation.
  • This finding provides a mechanistic explanation for the differing condensation behaviors of DNA and RNA.