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Interaction between microRNA-195 and HuR regulates Paneth cell function in the intestinal epithelium by altering SOX9

Min S Kwon1, Hee K Chung1, Lan Xiao1,2

  • 1Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, United States.

American Journal of Physiology. Cell Physiology
|August 5, 2024
PubMed

Insights

MicroRNA-195 (miR-195) represses Paneth cell function by inhibiting SOX9 translation through interaction with HuR. This discovery sheds light on the regulation of Paneth cell activity in the small intestine.

Area of Science:

  • Molecular Biology
  • Gastroenterology
  • Cell Biology

Background:

  • Paneth cells in the small intestine are crucial for pathogen clearance and maintaining the stem cell niche.
  • Paneth cell dysfunction is implicated in various diseases, but the regulatory mechanisms are poorly understood.
  • MicroRNAs (miRNAs) are known regulators of gene expression, but their specific roles in Paneth cell function require further investigation.

Purpose of the Study:

  • To identify novel regulators of Paneth cell development and function.
  • To elucidate the molecular mechanism by which microRNA-195 (miR-195) influences Paneth cell activity.
  • To investigate the role of SOX9 translation and its interaction with HuR in miR-195-mediated regulation.

Main Methods:

  • Generation of tissue-specific transgenic mice expressing miR-195 in the intestinal epithelium.
  • Analysis of Paneth cell numbers and SOX9 expression in wild-type and transgenic mice.
  • In vitro studies using intestinal organoids to assess the effects of SOX9 and miR-195 on Paneth cell development.
  • RNA immunoprecipitation and Western blotting to study the interaction between miR-195, HuR, and SOX9 mRNA.

Main Results:

  • Transgenic expression of miR-195 in mice led to decreased SOX9 levels and reduced Paneth cell numbers.
  • Ectopic SOX9 expression restored Paneth cell development in miR-195-expressing organoids.
  • miR-195 inhibited SOX9 translation by preventing HuR binding to SOX9 mRNA, without directly binding to the mRNA itself.
  • Inhibition of miR-195 activity improved Paneth cell function in HuR-deficient organoids.

Conclusions:

  • MicroRNA-195 acts as a repressor of Paneth cell development and function in the small intestinal epithelium.
  • The regulatory mechanism involves the interaction of miR-195 with HuR, leading to altered SOX9 translation.
  • These findings reveal a novel pathway controlling Paneth cell activity, with potential implications for intestinal diseases.
Keywords:
gut mucosal defenseintestinal epithelium homeostasisnoncoding RNAsposttranscriptional regulation

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