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Real-time Live Imaging of T-cell Signaling Complex Formation
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Published on: June 23, 2013

FasL expression in activated T lymphocytes involves HuR-mediated stabilization.

Gillian L Drury1, Sergio Di Marco, Virginie Dormoy-Raclet

  • 1Department of Biochemistry, Rosalind and Morris Goodman Cancer Center, Montreal, Quebec H3G 1Y6, Canada.

The Journal of Biological Chemistry
|August 3, 2010
PubMed
Summary

This study reveals how the RNA-binding protein HuR stabilizes Fas ligand (FasL) messenger RNA (mRNA) in T cells. This posttranscriptional regulation is crucial for controlling lymphocyte proliferation and maintaining immune tolerance.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Prolonged immune activation causes lymphocyte hyperproliferation, leading to autoimmune diseases.
  • Fas ligand (FasL) induces apoptosis in T cells, controlling excessive lymphoproliferation.

Purpose of the Study:

  • To investigate the posttranscriptional regulation of FasL expression.
  • To identify molecular mechanisms controlling FasL mRNA stability in activated T cells.

Main Methods:

  • Sequence analysis of the FasL 3'-untranslated region (UTR) for AU-rich elements (AREs).
  • In vitro and ex vivo complex formation assays between FasL mRNA and HuR.
  • Gene knockdown experiments using HEK 293 cells and a GFP reporter construct.

Main Results:

  • FasL mRNA is stable in activated T cells.
  • The FasL 3'-UTR contains AREs similar to TNFα mRNA.
  • HuR binds to FasL mRNA via these AREs.
  • HuR knockdown inhibits FasL 3'-UTR-mediated reporter gene expression.

Conclusions:

  • Posttranscriptional regulation by HuR is a novel mechanism modulating FasL expression.
  • HuR-mediated stabilization of FasL mRNA is critical for immune system function and tolerance.