title: Induction of the interferon-inducible RNA-degrading enzyme, RNase L, by stress-inducing agents in the human cervical carcinoma cells.
abstract: 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.
authors.affiliation: Molecular Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Mitali
authors.initials: M
authors.lastname: Pandey
authors.forename: Gagan Deep
authors.initials: GD
authors.lastname: Bajaj
authors.forename: Pramod C
authors.initials: PC
authors.lastname: Rath
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002122:Calcium Chloride / Q000494:pharmacology; D002277:Carcinoma / Q000201:enzymology*; D004722:Endoribonucleases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007372:Interferons / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D011070:Poly I-C / Q000494:pharmacology; D012313:RNA / Q000737:chemistry; D012330:RNA, Double-Stranded / Q000494:pharmacology; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000201:enzymology*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D012313:RNA; D007372:Interferons; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D002122:Calcium Chloride; D011070:Poly I-C