Increased endonuclease activity in an extract from mouse Ehrlich ascites tumor cells which had been treated with a partially purified interferon preparation: Dependence on double-stranded RNA

Brown, Gene M.; Lebleu, Bernard; Kawakita, Masao; Shaila, S.; Sen, Ganes C.; Lengyel, Péter

doi:10.1016/s0006-291x(76)80280-x

Cited by 118 publications

(23 citation statements)

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“…The initial and essential observation was made by Ian Kerr's group in 1974 reporting an IFN-induced increase in the sensitivity of protein synthesis to inhibition by dsRNA [3]. Peter Lengyel's group observed increased nuclease activity in extracts of interferon treated cells incubated with dsRNA [4,5]. The identification by Ian Kerr's group of the activators of this nuclease, 2-5A [6] and of the enzyme responsible for their synthesis, the 2-5A-synthetase [7][8][9], led to the discovery of the 2-5A pathway.…”

Section: I) Introductionmentioning

confidence: 99%

Diverse functions of RNase L and implications in pathology

Bisbal

Silverman

2007

Biochimie

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The endoribonuclease L (RNase L) is the effector of the 2-5A system, a major enzymatic pathway involved in the molecular mechanism of interferons (IFN). RNase L is a very unusual nuclease with a complex mechanism of regulation. It is a latent enzyme, expressed in nearly every mammalian cell type. Its activation requires its binding to a small oligonucleotide, 2-5A. 2-5A is a series of unique 5′-triphosphorylated oligoadenylates with 2′-5′ phosphodiester bonds. By regulating viral and cellular RNA expression, RNase L plays an important role in the antiviral and antiproliferative activities of IFN and contributes to innate immunity and cell metabolism. The 2-5A/RNase L pathway is implicated in mediating apoptosis in response to viral infections and to several types of external stimuli. Several recent studies have suggested that RNase L could have a role in cancer biology and evidence of a tumor suppressor function of RNase L has emerged from studies on the genetics of hereditary prostate cancer. KeywordsInterferon; RNase L; RNA expression; apoptosis; prostate; virus; cancer I) IntroductionThe endoribonuclease L (RNase L) is the effector of the 2-5A system, a major enzymatic pathway regulated by interferons (IFN) [1] (Figure 1). The 2-5A system is one of the two antiviral pathways induced by IFN and activated by double stranded RNA (dsRNA), the other is mediated by the dsRNA dependent protein kinase (PKR) [2]. RNase L is a very unusual nuclease. It is a latent enzyme, expressed in nearly every mammalian cell type. Its activation requires its binding to a small oligonucleotide, 2-5A ( Figure 1). 2-5A itself is very unusual, consisting of a series of 5′-triphosphorylated oligoadenylates with 2′-5′ phosphodiester bonds in contrast to the 3′-5′ linkages found in RNA and DNA. The initial and essential observation was made by Ian Kerr's group in 1974 reporting an IFN-induced increase in the sensitivity of protein synthesis to inhibition by dsRNA [3]. Peter Lengyel's group observed increased nuclease activity in extracts of interferon treated cells incubated with dsRNA [4,5]. The identification by Ian Kerr's group of the activators of this nuclease, 2-5A [6] and of the enzyme responsible for their synthesis, the 2-5A-synthetase [7][8][9], led to the discovery of the 2-5A pathway. Clemens and Williams directly demonstrated a nuclease, now recognized as RNase Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Figure 2). The N-terminal domain could be considered as the regulatory domain of RNase L. It is composed of eight complete and one partial ankyrin motifs (R1-R9). Two wal...

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Section: I) Introductionmentioning

confidence: 99%

Diverse functions of RNase L and implications in pathology

Bisbal

Silverman

2007

Biochimie

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“…IFN is induced by various factors, including viral infections, and is a cytokine possessing biological activities that include anti-viral, anti-tumor and immunomodulatory activities [1,2,6,8,11,12]. IFN induced by viral infections activates three enzymes-2'-phosphodiesterase, 2,5A-S and phosphokinase -which stimulate anti-viral activity via independent pathways [1].…”

Section: Discussionmentioning

confidence: 99%

“…IFN induced by viral infections activates three enzymes-2'-phosphodiesterase, 2,5A-S and phosphokinase -which stimulate anti-viral activity via independent pathways [1]. Among these enzymes, 2,5A-S has been employed in recent years as a parameter to base therapeutic efficacy of IFN in patients with hepatitis [2,6].…”

Section: Discussionmentioning

confidence: 99%

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Alpha-interferon for the treatment of idiopathic sudden sensorineural hearing loss

Kanemaru

Fukushima

Nakamura

et al. 1997

Eur Arch Otorhinolaryngol

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We have employed alpha-interferon (IFN-alpha), an anti-viral agent, in the treatment of severe idiopathic sudden sensorineural hearing loss (ISSHL). Forty-two patients were studied and had an average hearing ability of > or = 70 dB before treatment. We also examined 2'-5' oligoadenylate synthetase (2,5A-S) activity, one of the parameters indicating anti-viral activity of IFN, to investigate the relationship between the suppression of viral proliferation and prognosis and explain the pathogenesis of ISSHL. Complete recovery was found in 27 patients (64.3%) after IFN therapy. Increased 2,5A-S activity was observed on the 3rd day of IFN therapy in 24 of the 27 patients who completely recovered. No severe adverse events were reported after IFN therapy. Findings suggest that IFN therapy may be effective and safe in the treatment of ISSHL and calls for further investigation.

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“…Ian Kerr et ses collaborateurs ont été les premiers à observer une augmentation de l'inhibition de la synthèse des protéines en présence d'ARN double brin (ARNdb) dans des extraits de cellules traitées par l'IFN [3]. Cette première observation a permis de montrer que cette inhibition de la synthèse des protéines était due, entre autres, à la dégradation des ARN par une nucléase [4][5][6] dont l'activité était régulée par des petits oligonucléotides. Cette nucléase, nommée ensuite RNase L (L pour latente), est exprimée sous forme inactive dans presque toutes les cellules de mammifères.…”

Section: La Voie D'activation De La Rnase L Par Des Oligoadénylates 2-5aunclassified

La RNase L, un acteur essentiel de la réponse cellulaire antivirale

Bisbal

Salehzada

2008

Med Sci (Paris)

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Increased endonuclease activity in an extract from mouse Ehrlich ascites tumor cells which had been treated with a partially purified interferon preparation: Dependence on double-stranded RNA

Cited by 118 publications

References 24 publications

Diverse functions of RNase L and implications in pathology

Diverse functions of RNase L and implications in pathology

Alpha-interferon for the treatment of idiopathic sudden sensorineural hearing loss

La RNase L, un acteur essentiel de la réponse cellulaire antivirale

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