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

被引:38
作者
Al-Ahmadi, W. [1 ]
al-Haj, L. [1 ]
Al-Mohanna, F. A. [1 ]
Silverman, R. H. [2 ]
Khabar, K. S. A. [1 ,2 ]
机构
[1] King Faisal Specialist Hosp & Res Ctr, Program BioMol Res, Riyadh 11211, Saudi Arabia
[2] Cleveland Clin Fdn, Dept Canc Biol, Cleveland, OH 44195 USA
关键词
3 ' untranslated regions; RNase L; HuR; RNA-binding proteins; cell growth; DOUBLE-STRANDED-RNA; MESSENGER-RNA; PROGNOSTIC-FACTOR; PROSTATE-CANCER; RIBONUCLEASE-L; 3'-UNTRANSLATED REGION; INTERFERON RESPONSE; CELLS; EXPRESSION; KINASE;
D O I
10.1038/onc.2009.16
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 30 untranslated region (UTR), which harbors U-rich and adenylate-uridylate-rich elements, was potently responsive to RNase L when compared to control 30 UTR. Our results may offer a new explanation to the tumor suppressor function of RNase L.
引用
收藏
页码:1782 / 1791
页数:10
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