RNase L downmodulation of the RNA-binding protein, HuR, and cellular growth

W Al-Ahmadi1, L Al-Haj, F A Al-Mohanna

  • 1Program in BioMolecular Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Oncogene
|March 3, 2009
PubMed

Insights

Overexpressing Ribonuclease L (RNase L) inhibits cell growth and reduces the RNA-binding protein HuR. This suggests RNase L

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Ribonuclease L (RNase L) is an intracellular enzyme crucial for innate immunity.
  • RNase L is also investigated as a potential tumor suppressor.

Purpose of the Study:

  • To investigate the role of RNase L in cellular growth and its relationship with the RNA-binding protein HuR.
  • To explore the mechanism by which RNase L influences cell-cycle progression and tumorigenesis.

Main Methods:

  • Overexpression of RNase L in cells.
  • Comparison of RNase L-null mouse fibroblast lines with wild-type cells.
  • Analysis of HuR expression, cellular growth, and HuR mRNA stability.
  • Reporter assays using the HuR 3' untranslated region (UTR).

Main Results:

  • Overexpression of RNase L decreased cellular growth and downmodulated HuR.
  • RNase L's effect on cell growth and HuR was cell-cycle dependent and correlated with its cytoplasmic localization.
  • RNase L-null cells exhibited increased cellular growth and HuR levels, with enhanced HuR mRNA stability.
  • The HuR 3' UTR was sensitive to RNase L activity.

Conclusions:

  • RNase L negatively regulates cellular growth and HuR, a key regulator of cell-cycle progression.
  • The findings provide a potential mechanism for the tumor suppressor function of RNase L.

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