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Supramolecular Interactions Modulate RNA:DNA Folding Observed via Nanopore Sensing.

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Area of Science:

  • Biotechnology
  • Nanotechnology
  • Supramolecular Chemistry

Background:

  • DNA and RNA nanotechnology allow precise molecular assembly for bioengineering and sensing.
  • Material properties of biopolymers are tunable via covalent or non-covalent interactions.
  • Small molecules offer a simple method for modulating biopolymer properties.

Purpose of the Study:

  • To investigate the use of urea as a small molecule to modulate the stiffness of RNA:DNA hybrid nanostructures.
  • To assess the impact of urea on the structural properties and sensing applications of these nanostructures.

Main Methods:

  • Solid-state nanopore measurements to assess structural changes and translocation events.
  • Atomic force microscopy (AFM) to provide evidence of structural rigidification.
  • Preparation of topologically-barcoded RNA:DNA hybrids in the presence of urea.

Main Results:

  • Urea non-covalently interacts with the A-form-like helix of RNA:DNA hybrids, leading to rigidification.
  • Solid-state nanopore and AFM measurements confirmed the stiffening effect of urea.
  • Preparation in urea reduced folded translocation events by 50% in nanopore sensing experiments.

Conclusions:

  • Urea effectively modulates the stiffness of RNA:DNA hybrid nanostructures through supramolecular interactions.
  • The reduction in folded events enhances data quality for single-molecule detection.
  • This approach facilitates robust detection of low-abundance RNA analytes.