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

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.

SUBMITTER: Al-Ahmadi W

PROVIDER: S-EPMC3071643 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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

Al-Ahmadi W W Al-Haj L L Al-Mohanna F A FA Silverman R H RH Khabar K S A KS

Oncogene 20090302 15

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 fibrob ...[more]

PMID: 19252527

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