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AUF1 p42 isoform selectively controls both steady-state and PGE2-induced FGF9 mRNA decay

Tsung-Ming Chen1, Chien-Hui Hsu, Shaw-Jenq Tsai

  • 1Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.

Nucleic Acids Research
|August 19, 2010
PubMed

Insights

AU-rich element binding protein 1 (AUF1) controls Fibroblast Growth Factor 9 (FGF9) expression by regulating mRNA stability. The p42 isoform of AUF1 degrades FGF9 mRNA, impacting cellular homeostasis.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • RNA Metabolism

Background:

  • Fibroblast Growth Factor 9 (FGF9) is crucial for embryonic development and physiological processes.
  • Dysregulation of FGF9 expression is linked to human diseases, necessitating understanding its regulatory mechanisms.
  • The precise mechanisms controlling FGF9 expression remain largely unelucidated.

Purpose of the Study:

  • To investigate the role of AU-rich elements (AREs) in the 3'-untranslated region (UTR) of FGF9 mRNA in regulating gene expression.
  • To identify specific proteins that bind to the FGF9 ARE and influence its mRNA stability.
  • To elucidate the function of AU-rich element binding protein 1 (AUF1) isoforms in controlling FGF9 mRNA levels.

Main Methods:

  • Analysis of the FGF9 3'-UTR for the presence of AREs.
  • RNA immunoprecipitation assays to identify proteins binding to the FGF9 ARE.
  • Overexpression and knockdown studies of AUF1 isoforms (p37, p40, p42, p45) in cells.
  • mRNA stability assays (half-life measurements) for FGF9.
  • Treatment of human endometrial stromal cells with prostaglandin E2 (PGE2) and assessment of FGF9 and AUF1 levels.

Main Results:

  • An ARE in the FGF9 3'-UTR was identified as critical for controlling FGF9 expression.
  • AUF1 was shown to bind to this ARE, modulating FGF9 mRNA stability.
  • Only the p42 isoform of AUF1 significantly reduced steady-state FGF9 mRNA levels.
  • Knockdown of p42(AUF1) increased the half-life of FGF9 mRNA.
  • PGE2 treatment led to decreased cytoplasmic AUF1 and increased FGF9 mRNA, while AUF1 ablation caused sustained FGF9 elevation.

Conclusions:

  • The p42(AUF1) isoform regulates both basal and PGE2-induced FGF9 mRNA stability via ARE-mediated decay.
  • This study reveals a novel mechanism for controlling FGF9 expression through ARE-mediated mRNA degradation.
  • The findings suggest that ARE-mediated mRNA decay is a common pathway for regulating Fibroblast Growth Factor (FGF) family members, contributing to FGF homeostasis.

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