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Regulation of A + U-rich element-directed mRNA turnover involving reversible phosphorylation of AUF1

Gerald M Wilson1, Jiebo Lu, Kristina Sutphen

  • 1Department of Biochemistry and Molecular Biology and Center for Fluorescence Spectroscopy, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. gwils001@umaryland.edu

The Journal of Biological Chemistry
|June 24, 2003
PubMed

Insights

Signal pathways regulate mRNA decay by altering AUF1 protein phosphorylation. This impacts the stability of AU-rich element (ARE)-containing mRNAs, influencing inflammatory responses.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Proteins binding AU-rich elements (AREs) control mRNA turnover.
  • This process is regulated by signal transduction pathways and is crucial in inflammation.
  • Monocyte adherence inhibits ARE-directed mRNA decay, increasing inflammatory mediator production.

Purpose of the Study:

  • To investigate how signal transduction pathways regulate ARE-directed mRNA turnover.
  • To examine the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on ARE-containing mRNA stability and AUF1 activity in THP-1 cells.
  • To determine the role of p40AUF1 post-translational modifications in regulating mRNA turnover.

Main Methods:

  • Exposure of THP-1 monocytic leukemia cells to TPA.
  • Analysis of ARE-containing mRNA levels (interleukin-1 beta, tumor necrosis factor alpha).
  • Assessment of AUF1 protein activity and post-translational modifications (phosphorylation) in cytoplasmic complexes and polysomes.

Main Results:

  • TPA treatment mimicked monocyte adherence, inducing and stabilizing ARE-containing mRNAs.
  • TPA altered the activity of cytoplasmic ARE-binding complexes, including AUF1.
  • Post-translational modifications, specifically phosphorylation at Ser83 and Ser87, of p40AUF1 were altered by TPA treatment, correlating with changes in RNA binding and mRNA stabilization.

Conclusions:

  • Signal transduction pathways can regulate ARE-directed mRNA turnover.
  • Reversible phosphorylation of polysome-associated p40AUF1 is a potential mechanism for this regulation.
  • This mechanism may play a role in controlling inflammatory gene expression.

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