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Nucleic Acids Res. 2015 Jan;43(1):595-606. doi: 10.1093/nar/gku1311. Epub 2014 Dec 15.

Small antisense oligonucleotides against G-quadruplexes: specific mRNA translational switches.

Author information

1
RNA Group/Groupe ARN, Département de biochimie, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée sur le cancer, Université de Sherbrooke, Québec, J1E 4K8, Canada.
2
RNA Group/Groupe ARN, Département de biochimie, Faculté de médecine et des sciences de la santé, Pavillon de recherche appliquée sur le cancer, Université de Sherbrooke, Québec, J1E 4K8, Canada jean-pierre.perreault@usherbrooke.ca.

Abstract

G-quadruplexes (G4) are intricate RNA structures found throughout the transcriptome. Because they are associated with a variety of biological cellular mechanisms, these fascinating structural motifs are seen as potential therapeutic targets against many diseases. While screening of chemical compounds specific to G4 motifs has yielded interesting results, no single compound successfully discriminates between G4 motifs based on nucleotide sequences alone. This level of specificity is best attained using antisense oligonucleotides (ASO). Indeed, oligonucleotide-based strategies are already used to modulate DNA G4 folding in vitro. Here, we report that, in human cells, the use of short ASO to promote and inhibit RNA G4 folding affects the translation of specific mRNAs, including one from the 5'UTR of the H2AFY gene, a histone variant associated with cellular differentiation and cancer. These results suggest that the relatively high specificity of ASO-based strategies holds significant potential for applications aimed at modulating G4-motif folding.

PMID:
25510493
PMCID:
PMC4288198
DOI:
10.1093/nar/gku1311
[Indexed for MEDLINE]
Free PMC Article

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