Control of the polyamine biosynthesis pathway by G2-quadruplexes

Elife. 2018 Jul 31:7:e36362. doi: 10.7554/eLife.36362.


G-quadruplexes are naturally-occurring structures found in RNAs and DNAs. Regular RNA G-quadruplexes are highly stable due to stacked planar arrangements connected by short loops. However, reports of irregular quadruplex structures are increasing and recent genome-wide studies suggest that they influence gene expression. We have investigated a grouping of G2-motifs in the UTRs of eight genes involved in polyamine biosynthesis, and concluded that several likely form novel metastable RNA G-quadruplexes. We performed a comprehensive biophysical characterization of their properties, comparing them to a reference G-quadruplex. Using cellular assays, together with polyamine-depleting and quadruplex-stabilizing ligands, we discovered how some of these motifs regulate and sense polyamine levels, creating feedback loops during polyamine biosynthesis. Using high-resolution 1H-NMR spectroscopy, we demonstrated that a long-looped quadruplex in the AZIN1 mRNA co-exists in salt-dependent equilibria with a hairpin structure. This study expands the repertoire of regulatory G-quadruplexes and demonstrates how they act in unison to control metabolite homeostasis.

Keywords: NMR; RNA; biochemistry; chemical biology; human; polyamine; pyridostatin; quadruplex; thioflavin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • DNA / chemistry*
  • DNA / genetics
  • G-Quadruplexes*
  • Gene Expression Regulation / genetics
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Polyamines / chemistry
  • Polyamines / metabolism*
  • RNA / chemistry
  • RNA / genetics


  • 5' Untranslated Regions
  • AZIN1 protein, human
  • Carrier Proteins
  • Ligands
  • Polyamines
  • RNA
  • DNA