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

Oncogene volume 28, pages 1782–1791 (2009)Cite this article

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.

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Acknowledgements

We thank Dr Myriam Gorospe for critical reading of the paper. We also thank Dr A Aboussekhra for his valuable comments on cell-cycle experiments. We also appreciate the staff at the flow cytometry facility for their technical assistance. The assistance of Dr P Mohideen, Mr Maher Al-Saif, and Mr Fahad Al-Zoghaibi in cloning of the 3′ UTR is appreciated. We especially thank Dr Hitti for his help with real-time primer/probe design. We are also indebted to the King Faisal Specialist Hospital and Research Center Subsidiary in Maryland, USA for managing and expediting reagent and supplies purchases for this study.

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Authors and Affiliations

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

    W Al-Ahmadi, L al-Haj, F A Al-Mohanna & K S A Khabar

  2. Department of Cancer Biology, Cleveland Clinic Foundation, Cleveland, OH, USA

    R H Silverman & K S A Khabar

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  1. W Al-Ahmadi
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Correspondence to K S A Khabar.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Al-Ahmadi, W., al-Haj, L., Al-Mohanna, F. et al. RNase L downmodulation of the RNA-binding protein, HuR, and cellular growth. Oncogene 28, 1782–1791 (2009). https://doi.org/10.1038/onc.2009.16

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