RNase L downmodulation of the RNA-binding protein, HuR, and cellular growth.
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.
Al-Ahmadi
W
W
Program in BioMolecular Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Al-Haj
L
L
Al-Mohanna
F A
FA
Silverman
R H
RH
Khabar
K S A
KS
D020413:3' Untranslated Regions / Q000502:physiology; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D002453:Cell Cycle; D049109:Cell Proliferation; D015536:Down-Regulation; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D004722:Endoribonucleases / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
D020413:3' Untranslated Regions; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease