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Published on: June 16, 2022
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.
Abstract:
Ribonuclease L (RNase L) is an intracellular enzyme that is vital in innate immunity, but also is a tumor suppressor candidate. Here, we show that overexpression of RNase L decreases cellular growth and downmodulates the RNA-binding protein, HuR, a regulator of cell-cycle progression and tumorigenesis. The effect is temporal, occurring in specific cell-cycle phases and correlated with the cytoplasmic localization of RNase L. Both cellular growth and HuR were increased in RNASEL-null mouse fibroblast lines when compared to wild-type cells. Moreover, the stability of HuR mRNA was enhanced in RNASEL-null cells. The HuR 3' untranslated region (UTR), which harbors U-rich and adenylate-uridylate-rich elements, was potently responsive to RNase L when compared to control 3' UTR. Our results may offer a new explanation to the tumor suppressor function of RNase L.
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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