The Human Interferon- and Estrogen-Regulated <i>ISG20/HEM45</i> Gene Product Degrades Single-Stranded RNA and DNA in Vitro

Nguyen, Lam H.; Espert, Lucile; Mechti, Nadir; Wilson, David M.

doi:10.1021/bi010141t

Cited by 94 publications

(139 citation statements)

References 25 publications

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…In accordance with this information, a site-specific aspartate to glycine residue mutation in the ExoII conserved motif of ISG20 (mut-ISG20D94G; Fig. 1A) abolished its activity (24). Because IFN causes a strong induction of ISG20 expression (21,29), these data suggested that the protein could be an active player in the antiviral action mediated by IFNs against RNA viruses.…”

Section: Isg20 Confers Resistance To Vsv Infection In Transientlysupporting

confidence: 65%

“…Based on these observations, we have demonstrated that ISG20 is a 3Ј to 5Ј exonuclease in vitro with specificity for single-stranded RNA and, to a lesser extent, for DNA, suggesting that ISG20 could be involved in the antiviral function of IFN against RNA viruses (24). Notably, ISG20 is the second known RNase regulated by IFN, along with RNase L (24).…”

Section: Interferons (Ifns)mentioning

confidence: 81%

“…The cDNA encoding the inactive ISG20 mutant protein was generated by sitespecific mutation in the conserved ExoII motif (24) and subsequently cloned into the pCiNeo vector to generate the pCiNeo-mut-ISG20 expression vector. For the transient transfection experiments, the cDNAs coding for wt-ISG20 and mut-ISG20 protein were subcloned into the pEGFP vector in the same open reading frame as the GFP to generate the pGFP-wt-ISG20 and pGFP-mut-ISG20 expression vector, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Transfected HeLa Cells-We have shown previously that ISG20 is a 3Ј to 5Ј exonuclease that specifically degrades in vitro single-stranded RNA substrates (and, to a lesser extent, single-stranded DNA substrates) (24). Homology within the superfamily is concentrated at three conserved exonuclease motifs termed ExoI, ExoII, and ExoIII (23).…”

Section: Isg20 Confers Resistance To Vsv Infection In Transientlymentioning

confidence: 99%

See 3 more Smart Citations

ISG20, a New Interferon-induced RNase Specific for Single-stranded RNA, Defines an Alternative Antiviral Pathway against RNA Genomic Viruses

Espert

Degols

Gongora

et al. 2003

Journal of Biological Chemistry

Self Cite

199

196

View full text Add to dashboard Cite

Interferons (IFNs) encode a family of secreted proteins that provide the front-line defense against viral infections. Their diverse biological actions are thought to be mediated by the products of specific but usually overlapping sets of cellular genes induced in the target cells. We have recently isolated a new human IFN-induced gene that we have termed ISG20, which codes for a 3 to 5 exonuclease with specificity for single-stranded RNA and, to a lesser extent, for DNA. In this report, we demonstrate that ISG20 is involved in the antiviral functions of IFN. In the absence of IFN treatment, ISG20-overexpressing HeLa cells showed resistance to infections by vesicular stomatitis virus (VSV), influenza virus, and encephalomyocarditis virus (three RNA genomic viruses) but not to the DNA genomic adenovirus. ISG20 specifically interfered with VSV mRNA synthesis and protein production while leaving the expression of cellular control genes unaffected. No antiviral effect was observed in cells overexpressing a mutated ISG20 protein defective in exonuclease activity, demonstrating that the antiviral effects were due to the exonuclease activity of ISG20. In addition, the inactive mutant ISG20 protein, which is able to inhibit ISG20 exonuclease activity in vitro, significantly reduced the ability of IFN to block VSV development. Taken together, these data suggested that the antiviral activity of IFN against VSV is partly mediated by ISG20. We thus show that, besides RNase L, ISG20 has an antiviral activity, supporting the idea that it might represent a novel antiviral pathway in the mechanism of IFN action. Interferons (IFNs)1 are a family of multifunctional secreted proteins characterized by their abilities to interfere with virus infection and replication (1, 2). IFNs can indirectly inhibit viral production by reducing the growth of target cells and by stimulating their susceptibility to apoptotic processes (3, 4) or by promoting the recognition and the cytotoxic killing of infected cells by the immune system (5, 6). IFNs also act directly at various steps of the viral multiplication cycle through the products of specific but usually overlapping sets of cellular genes induced in the target cells and involved in RNA and protein metabolism and signaling as well (7,8). Until now, three IFNregulated pathways have been considered to be involved in these processes: the double-stranded RNA-dependent protein kinase R (PKR) (9 -11), the 2-5A/RNase L system (12, 13), and the Mx proteins (14 -16). PKR is a serine/threonine kinase that, after binding to dsRNA, phosphorylates the protein synthesis initiation factor eIF2 and the inhibitor of nuclear factor B (IB), resulting in the inhibition of protein synthesis and specific transcription regulation (reviewed in . RNase L is a dormant cytosolic endoribonuclease that is activated by short oligoadenylates produced by the 2Ј-5Ј oligoadenylate synthetase after viral infection or IFN exposure (reviewed in Refs. 2 and 13). Degradation of viral RNAs and cleavage of cellular 18 S and 28 S rRNA...

show abstract

Section: Isg20 Confers Resistance To Vsv Infection In Transientlysupporting

confidence: 65%

Section: Interferons (Ifns)mentioning

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Section: Isg20 Confers Resistance To Vsv Infection In Transientlymentioning

confidence: 99%

See 2 more Smart Citations

ISG20, a New Interferon-induced RNase Specific for Single-stranded RNA, Defines an Alternative Antiviral Pathway against RNA Genomic Viruses

Espert

Degols

Gongora

et al. 2003

Journal of Biological Chemistry

Self Cite

199

196

View full text Add to dashboard Cite

show abstract

“…Mutations in the ISRE result in the loss of IFN type I and type II inducibility of the luciferase reporter gene (Gongora et al, 2000). Interestingly, it has been reported that ISG20 is a 3' to 5' exonuclease in vitro with speci®city for single stranded RNA and, to a lesser extent, for DNA (Nguyen et al, 2001). Notably, ISG20 is the second known RNase regulated by IFN, along with RNase L. In addition, over-expression of ISG20 confers resistance to infections by some RNA viruses (N Mechti, personal communication).…”

Section: Isg20mentioning

confidence: 99%

Role and fate of PML nuclear bodies in response to interferon and viral infections

2001

View full text Add to dashboard Cite

Interferons (IFNs) are a family of secreted proteins with antiviral, antiproliferative and immunomodulatory activities. The di erent biological actions of IFN are believed to be mediated by the products of speci®cally induced cellular genes in the target cells. The promyelocytic leukaemia (PML) protein localizes both in the nucleoplasm and in matrix-associated multi-protein complexes known as nuclear bodies (NBs). PML is essential for the proper formation and the integrity of the NBs. Modi®cation of PML by the Small Ubiquitin MOdi®er (SUMO) was shown to be required for its localization in NBs. The number and the intensity of PML NBs increase in response to interferon (IFN). Inactivation of the IFN-induced PML gene by its fusion to retinoic acid receptor alpha alters the normal localization of PML from the punctuate nuclear patterns of NBs to microdispersed tiny dots and results in uncontrolled growth in Acute Promyelocytic Leukaemia. The NBs-associated proteins, PML, Sp100, Sp140, Sp110, ISG20 and PA28 are induced by IFN suggesting that nuclear bodies could play a role in IFN response. Although the function of PML NBs is still unclear, some results indicate that they may represent preferential targets for viral infections and that PML could play a role in the mechanism of the antiviral action of IFNs. Viruses, which require the cellular machinery for their replication, have evolved di erent ways to counteract the action of IFN by inhibiting IFN signalling, by blocking the activities of speci®c antiviral mediators or by altering PML expression and/or localization on nuclear bodies. Oncogene (2001) 20, 7274 ± 7286.

show abstract

ISG20: an enigmatic antiviral RNase targeting multiple viruses

et al. 2022

View full text Add to dashboard Cite

Interferon‐stimulated gene 20 kDa protein (ISG20) is a relatively understudied antiviral protein capable of inhibiting a broad spectrum of viruses. ISG20 exhibits strong RNase properties, and it belongs to the large family of DEDD exonucleases, present in both prokaryotes and eukaryotes. ISG20 was initially characterized as having strong RNase activity in vitro, suggesting that its inhibitory effects are mediated via direct degradation of viral RNAs. This mechanism of action has since been further elucidated and additional antiviral activities of ISG20 highlighted, including direct degradation of deaminated viral DNA and translational inhibition of viral RNA and nonself RNAs. This review focuses on the current understanding of the main molecular mechanisms of viral inhibition by ISG20 and discusses the latest developments on the features that govern specificity or resistance to its action.

show abstract

The Human Interferon- and Estrogen-Regulated ISG20/HEM45 Gene Product Degrades Single-Stranded RNA and DNA in Vitro

Cited by 94 publications

References 25 publications

ISG20, a New Interferon-induced RNase Specific for Single-stranded RNA, Defines an Alternative Antiviral Pathway against RNA Genomic Viruses

ISG20, a New Interferon-induced RNase Specific for Single-stranded RNA, Defines an Alternative Antiviral Pathway against RNA Genomic Viruses

Role and fate of PML nuclear bodies in response to interferon and viral infections

ISG20: an enigmatic antiviral RNase targeting multiple viruses

Contact Info

Product

Resources

About