Document Detail

RNase L downmodulation of the RNA-binding protein, HuR, and cellular growth.
MedLine Citation:
PMID:  19252527     Owner:  NLM     Status:  MEDLINE    
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.
W Al-Ahmadi; L Al-Haj; F A Al-Mohanna; R H Silverman; K S A Khabar
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Publication Detail:
Type:  Journal Article     Date:  2009-03-02
Journal Detail:
Title:  Oncogene     Volume:  28     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-16     Completed Date:  2009-04-28     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  1782-91     Citation Subset:  IM    
Program in BioMolecular Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
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MeSH Terms
3' Untranslated Regions / physiology
Antigens, Surface / genetics
Cell Cycle
Cell Proliferation
Endoribonucleases / physiology*
HeLa Cells
Mice, Inbred C57BL
RNA, Messenger / analysis
RNA-Binding Proteins / antagonists & inhibitors*,  genetics
Grant Support
R01 CA044059/CA/NCI NIH HHS; R01 CA044059-26/CA/NCI NIH HHS
Reg. No./Substance:
0/3' Untranslated Regions; 0/Antigens, Surface; 0/ELAVL1 protein, human; 0/RNA, Messenger; 0/RNA-Binding Proteins; EC 3.1.-/Endoribonucleases; EC 3.1.26.-/2-5A-dependent ribonuclease

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