Induction of the interferon-inducible RNA-degrading enzyme, RNase L, by stress-inducing agents in the human cervical carcinoma cells

RNA Biol. 2004 May;1(1):21-7. Epub 2004 May 5.


RNA-degradation is one of the fundamental mechanisms of interferon (IFN)-inducible antiviral response in mammalian cells. This is primarily brought about by the IFN-inducible 2',5'-oligoadenylate (2-5A)-cofactor dependent ribonuclease L (RNase L). RNase L also functions as a tumor suppressor gene in case of prostate cancer due to its role in apoptosis. We report that RNase L is induced by stress-inducing agents such as double-stranded RNA [poly(I:C)], chemotherapeutic drugs, hydrogen peroxide (H(2)O(2)), calcium chloride (CaCl(2)) and tumor necrosis factor-alpha (TNF) in the human cervical carcinoma (HeLa) cells. The level of RNase L was not detected in the untreated cells. Induction of RNase L by such stress-inducing agents correlated with degradation of cellular RNA, fragmentation of chromatin-DNA and induction of apoptosis. We checked the stress-inducible transcription factor, nuclear factor kappa B (NF-kappaB), which was persistently activated by cycloheximide but not by other agents after 24 hours indicating no role of NFkappaB in the RNase L-induction. However, as expected, TNF-induced NF-kappaB activity was stimulated within 10-30 minutes through degradation of IkappaB-alpha. Our results strongly suggest that the IFN-inducible RNase L is induced by a broad range of stress-inducing signals such as double-stranded RNA (dsRNA) produced during viral infection, membrane- and osmotic shock caused by CaCl(2) and oxidative stress induced by H(2)O(2), inflammation stimulated by TNF-alpha and chemotherapy. Thus, in addition to its antiviral function, the IFN-inducible RNase L may play an important role during stress-response through RNA-degradation and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Calcium Chloride / pharmacology
  • Carcinoma / enzymology*
  • Endoribonucleases / metabolism*
  • Female
  • Humans
  • Interferons / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress
  • Poly I-C / pharmacology
  • RNA / chemistry
  • RNA, Double-Stranded / pharmacology
  • Time Factors
  • Uterine Cervical Neoplasms / enzymology*


  • Antineoplastic Agents
  • NF-kappa B
  • RNA, Double-Stranded
  • RNA
  • Interferons
  • Endoribonucleases
  • 2-5A-dependent ribonuclease
  • Calcium Chloride
  • Poly I-C