Control of the polyamine biosynthesis pathway by G2-quadruplexes

eLife

Frédéric Hai-Trieu Allain¹  Antoine Cléry²  Jonathan Hall²  Timo Hagen³  Helen Louise Lightfoot³ 

[1] Biomolecular NMR spectroscopy platform, ETH Zurich, Zurich, Switzerland;Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland;Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland;

关键词: polyamine;    RNA;    quadruplex;    NMR;    pyridostatin;    thioflavin;   

DOI  :  10.7554/eLife.36362

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown