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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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G-Quadruplexes influence pri-microRNA processing.

Samuel G Rouleau1, Jean-Michel Garant1, François Bolduc1

  • 1a Département de Biochimie, Pavillon de Recherche Appliquée sur le Cancer , Université de , Sherbrooke, 3201 Jean-Mignault, Sherbrooke , Québec , Canada.

RNA Biology
|November 25, 2017
PubMed
Summary
This summary is machine-generated.

RNA G-Quadruplexes (G4) regulate microRNA (miRNA) processing by affecting pri-miRNA cleavage. Disrupting G4 structures alters mature miRNA levels, highlighting their therapeutic potential.

Keywords:
Antisense OligonucleotideG-QuadruplexbiogenesismiRNAmicroRNAmir200cmir451amir497pri-miRNA processing

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Area of Science:

  • Molecular Biology
  • RNA Biology
  • Genetics

Background:

  • RNA G-Quadruplexes (G4) are known to regulate microRNA (miRNA) biogenesis and function.
  • The specific impact of G4 structures on primary miRNA (pri-miRNA) processing has not been previously elucidated.

Purpose of the Study:

  • To investigate the role of G4 motifs in pri-miRNA processing.
  • To determine if G4 structures influence the cleavage of pri-miRNAs by Drosha.
  • To explore the potential of G4 motifs as therapeutic targets for miRNA regulation.

Main Methods:

  • Identification of G4 motifs near Drosha cleavage sites in pri-mir200c, pri-mir451a, and pri-mir497.
  • Determination of G4 motif folding in solution using biophysical techniques.
  • Mutation analysis of G4 motifs to assess their impact on mature miRNA levels in cellular contexts.
  • Application of antisense oligonucleotides to modulate pri-miRNA processing and mature miRNA levels.

Main Results:

  • G4 motifs were identified near the Drosha cleavage site in specific pri-miRNAs.
  • Disruption of G4 folding significantly altered mature miRNA levels in cells.
  • Antisense oligonucleotides targeting pri-miRNAs could modulate mature miRNA production.
  • These findings suggest G4 motifs regulate pri-miRNA processing.

Conclusions:

  • G4 motifs play a novel role in regulating pri-miRNA processing, impacting mature miRNA levels.
  • The presence of G4 motifs in a significant percentage of pri-miRNAs suggests broad regulatory potential.
  • G4 structures represent promising targets for future therapeutic strategies aimed at modulating miRNA levels.