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Nat Chem. 2014 Jan;6(1):75-80. doi: 10.1038/nchem.1805. Epub 2013 Nov 24.

Visualization and selective chemical targeting of RNA G-quadruplex structures in the cytoplasm of human cells.

Author information

1
Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
2
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
3
1] Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK [2] Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.

Abstract

Following extensive evidence for the formation of four-stranded DNA G-quadruplex structures in vitro, DNA G-quadruplexes have been observed within human cells. Although chemically distinct, RNA can also fold in vitro into G-quadruplex structures that are highly stable because of the 2'-hydroxyl group. However, RNA G-quadruplexes have not yet been reported in cells. Here, we demonstrate the visualization of RNA G-quadruplex structures within the cytoplasm of human cells using a G-quadruplex structure-specific antibody. We also demonstrate that small molecules that bind to G-quadruplexes in vitro can trap endogenous RNA G-quadruplexes when applied to cells. Furthermore, a small molecule that exhibits a preference for RNA G-quadruplexes rather than DNA G-quadruplexes in biophysical experiments also shows the same selectivity within a cellular context. Our findings provide substantive evidence for RNA G-quadruplex formation in the human transcriptome, and corroborate the selectivity and application of stabilizing ligands that target G-quadruplexes within a cellular context.

PMID:
24345950
PMCID:
PMC4081541
DOI:
10.1038/nchem.1805
[Indexed for MEDLINE]
Free PMC Article

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