核糖核酸酶L对RNA结合蛋白HuR及细胞生长的下调作用
RNase L downmodulation of the RNA-binding protein, HuR, and cellular growth.
作者信息
Al-Ahmadi W, Al-Haj L, Al-Mohanna F A, Silverman R H, Khabar K S A
机构信息
Program in BioMolecular Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
出版信息
Oncogene. 2009 Apr 16;28(15):1782-91. doi: 10.1038/onc.2009.16. Epub 2009 Mar 2.
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.
摘要
核糖核酸酶L（RNase L）是一种细胞内酶，在先天免疫中至关重要，也是一种肿瘤抑制候选因子。在此，我们表明RNase L的过表达会降低细胞生长，并下调RNA结合蛋白HuR，HuR是细胞周期进程和肿瘤发生的调节因子。这种作用具有时间性，发生在特定的细胞周期阶段，并且与RNase L的细胞质定位相关。与野生型细胞相比，RNASEL基因敲除的小鼠成纤维细胞系中的细胞生长和HuR均增加。此外，RNASEL基因敲除细胞中HuR mRNA的稳定性增强。与对照3'非翻译区（UTR）相比，含有富含U和富含腺苷酸-尿苷酸元件的HuR 3'UTR对RNase L有强烈反应。我们的结果可能为RNase L的肿瘤抑制功能提供新的解释。
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