Journal
RNA BIOLOGY
Volume 15, Issue 2, Pages 198-206Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2017.1405211
Keywords
Antisense Oligonucleotide; biogenesis; mir200c; mir451a; mir497; microRNA; G-Quadruplex; miRNA; pri-miRNA processing
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Funding
- Natural Science and Engineering Research Council (NSERC) of Canada
- Chaire de recherche de l'Universite de Sherbrooke en Structure et Genomique de l'ARN
- Fonds de Recherche du Quebec - Nature et Technologie (FRQ-NT)
- Universite de Sherbrooke
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RNA G-Quadruplexes (G4) have been shown to possess many biological functions, including the regulation of microRNA (miRNA) biogenesis and function. However, their impact on pri-miRNA processing remains unknown. We identified G4 located near the Drosha cleavage site in three distinct pri-miRNAs: pri-mir200c, pri-mir451a, and pri-mir497. The folding of the potential G4 motifs was determined in solution. Subsequently, mutations disrupting G4 folding led to important changes in the mature miRNAs levels in cells. Moreover, using small antisense oligonucleotides binding to the pri-miRNA, it was possible to modulate, either positively or negatively, the mature miRNA levels. Together, these data demonstrate that G4 motifs could contribute to the regulation of pri-mRNA processing, a novel role for G4. Considering that bio-informatics screening indicates that between 9% and 50% of all pri-miRNAs contain a putative G4, these structures possess interesting potential as future therapeutic targets.
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