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Updated: Jun 12, 2025

Biotin-based Pulldown Assay to Validate mRNA Targets of Cellular miRNAs
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Mature microRNA-binding protein QKI suppresses extracellular microRNA let-7b release.

Kyung-Won Min1,2, Kyoung-Min Choi3, Hyejin Mun3

  • 1Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.

Journal of Cell Science
|September 23, 2024
PubMed
Summary

Quaking (QKI) protein limits brain inflammation by controlling extracellular release of microRNA let-7b. Depleting QKI enhances let-7b release, activating inflammatory pathways in recipient cells.

Keywords:
AGO2Extracellular vesicular miRNAQKIRNA-binding proteinlet-7b

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Area of Science:

  • Molecular Biology
  • Neuroscience
  • Immunology

Background:

  • Argonaute (AGO) proteins are key in RNA-induced silencing complexes (RISCs) for post-transcriptional gene silencing.
  • The roles of other miRNA-binding proteins (miRBPs) in miRNA regulation, including extracellular release, are not well understood.

Purpose of the Study:

  • To identify novel miRNA-binding proteins (miRBPs) and elucidate their function in miRNA regulation.
  • To investigate the role of quaking (QKI) in the regulation of extracellular microRNA release and its impact on inflammation.

Main Methods:

  • Utilized protein arrays to profile miRNA-binding proteins (miRBPs).
  • Identified 118 RBPs that directly bind to miRNAs.
  • Investigated the effect of QKI depletion on extracellular let-7b release and subsequent inflammatory responses in a mouse model.

Main Results:

  • Identified 118 RBPs that directly bind to miRNAs.
  • Discovered that quaking (QKI) inhibits the extracellular release of microRNA let-7b by regulating its loading into extracellular vesicles.
  • QKI depletion led to increased extracellular let-7b, activating Toll-like receptor 7 (TLR7) and promoting pro-inflammatory cytokine production, causing brain inflammation.

Conclusions:

  • Quaking (QKI) acts as a crucial regulator of extracellular microRNA let-7b release.
  • QKI's regulation of let-7b release is vital for suppressing brain inflammation.
  • This study highlights a novel mechanism linking miRNA regulation to neuroinflammation.