Specific suppression of D-RNA G-quadruplex-protein interaction with an L-RNA aptamer

Nucleic Acids Res. 2020 Oct 9;48(18):10125-10141. doi: 10.1093/nar/gkaa759.


G-quadruplexes (G4s) are nucleic acid structure motifs that are of significance in chemistry and biology. The function of G4s is often governed by their interaction with G4-binding proteins. Few categories of G4-specific tools have been developed to inhibit G4-protein interactions; however, until now there is no aptamer tool being developed to do so. Herein, we present a novel L-RNA aptamer that can generally bind to D-RNA G-quadruplex (rG4) structure, and interfere with rG4-protein interaction. Using hTERC rG4 as the target for in vitro selection, we report the shortest L-aptamer being developed so far, with only 25 nucleotides. Notably, this new aptamer, L-Apt.4-1c, adopts a stem-loop structure with the loop folding into an rG4 motif with two G-quartet, demonstrates preferential binding toward rG4s over non-G4s and DNA G-quadruplexes (dG4s), and suppresses hTERC rG4-nucleolin interactions. We also show that inhibition of rG4-protein interaction using L-RNA aptamer L-Apt.4-1c is comparable to or better than G4-specific ligands such as carboxypyridostatin and QUMA-1 respectively, highlighting that our approach and findings expand the current G4 toolbox, and open a new avenue for diverse applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide / chemical synthesis
  • Aptamers, Nucleotide / chemistry*
  • Aptamers, Nucleotide / metabolism*
  • G-Quadruplexes*
  • Humans
  • Phosphoproteins / metabolism*
  • Protein Binding
  • RNA* / chemistry
  • RNA* / metabolism
  • RNA-Binding Proteins / metabolism*
  • Telomerase* / chemistry
  • Telomerase* / metabolism


  • Aptamers, Nucleotide
  • Phosphoproteins
  • RNA-Binding Proteins
  • nucleolin
  • telomerase RNA
  • RNA
  • Telomerase