Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

The exonuclease ISG20 is directly induced by synthetic dsRNA via NF-κB and IRF1 activation

Oncogene volume 23, pages 4636–4640 (2004)Cite this article

Abstract

Many interferon (IFN)-stimulated genes are also induced by double-stranded RNA (dsRNA), a component closely associated with the IFN system in the context of virus–host interactions. Recently, we demonstrated that the IFN-induced 3′ → 5′ exonuclease ISG20 possesses antiviral activities against RNA viruses. Here we show that ISG20 induction by synthetic dsRNA (pIpC) is stronger and faster than its induction by IFN. Two families of transcription factors are implicated in the transcriptional activation of ISG20 by dsRNA. Initially, the NF-κB factors p50 and p65 bind and activate the κB element of the Isg20 promoter. This is followed by IRF1 binding to the ISRE. As pIpC often induces protein movements in the cells, we questioned whether it could influence ISG20 localization. Interestingly and contrary to IFN, dsRNA induces a nuclear matrix enrichment of the ISG20 protein. dsRNA induction of ISG20 via NF-κB and its antiviral activity led us to suggest that ISG20 could participate in the cellular response to virus infection.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Alexopoulou L, Holt AC, Medzhitov R and Flavell RA . (2001). Nature, 413, 732–738.

  • Amundson SA, Myers TG and Fornace Jr AJ . (1998). Oncogene, 17, 3287–3299.

  • Bandyopadhyay SK, Leonard Jr GT, Bandyopadhyay T, Stark GR and Sen GC . (1995). J. Biol. Chem., 270, 19624–19629.

  • Behr M, Schieferdecker K, Buhr P, Buter M, Petsophonsakul W, Sirirungsi W, Redmann-Muller I, Muller U, Prempracha N and Jungwirth C . (2001). J. Interferon Cytokine Res., 21, 981–990.

  • Blair LA, Maggi Jr LB, Scarim AL and Corbett JA . (2002). J. Biol. Chem., 277, 359–365.

  • Diaz-Guerra M, Rivas C and Esteban M . (1997). Virology, 236, 354–363.

  • Deppert W . (2000). Crit. Rev. Eukaryot. Gene Exp., 10, 45–61.

  • Doyle S, Vaidya S, O'Connell R, Dadgostar H, Dempsey P, Wu T, Rao G, Sun R, Haberland M, Modlin R and Cheng G . (2002). Immunity, 17, 251–263.

  • Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K and Tuschl T . (2001). Nature, 411, 494–498.

  • Espert L, Degols G, Gongora C, Blondel D, Williams BR, Silverman RH and Mechti N . (2003). J. Biol. Chem., 278, 16151–16158.

  • Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, Coyle AJ, Liao SM and Maniatis T . (2003). Nat. Immunol., 4, 491–496.

  • Geiss G, Jin G, Guo J, Bumgarner R, Katze MG and Sen GC . (2001). J. Biol. Chem., 276, 30178–30182.

  • Gongora C, David G, Pintard L, Tissot C, Hua TD, Dejean A and Mechti N . (1997). J. Biol. Chem., 272, 19457–19463.

  • Gongora C, Degols G, Espert L, Hua TD and Mechti N . (2000). Nucleic Acids Res., 28, 2333–2341.

  • Hummer BT, Li XL and Hassel BA . (2001). J. Virol., 75, 7774–7777.

  • Iordanov MS, Paranjape JM, Zhou A, Wong J, Williams BR, Meurs EF, Silverman RH and Magun BE . (2000). Mol. Cell. Biol., 20, 617–627.

  • Iordanov MS, Wong J, Bell JC and Magun BE . (2001). Mol. Cell. Biol., 21, 61–72.

  • Jacobs BL and Langland JO . (1996). Virology, 219, 339–349.

  • Kaufman RJ . (1999). Proc. Natl. Acad. Sci. USA, 96, 11693–11695.

  • Kehoe KE, Brown MA and Imani F . (2001). J. Immunol., 167, 2496–2501.

  • Mori K, Yoshida K, Tani J, Nakagawa Y, Hoshikawa S and Ito S . (2001). Mol. Cell Endocrinol., 184, 77–86.

  • Nguyen LH, Espert L, Mechti N and Wilson III DM . (2001). Biochemistry, 40, 7174–7179.

  • Okorokov AL, Rubbi CP, Metcalfe S and Milner J . (2002). Oncogene, 21, 356–367.

  • Peters KL, Smith HL, Stark GR and Sen GC . (2002). Proc. Natl. Acad. Sci. USA, 99, 6322–6327.

  • Roti Roti JL, Wright WD and VanderWaal R . (1997). Crit. Rev. Eukaryot. Gene Exp., 7, 343–360.

  • Samuel CE . (2001). Clin. Microbiol. Rev., 14, 778–809 table of contents.

  • Saura M, Zaragoza C, Bao C, McMillan A and Lowenstein CJ . (1999). J. Mol. Biol., 289, 459–471.

  • Sharma S, tenOever BR, Grandvaux N, Zhou GP, Lin R and Hiscott J . (2003). Science, 300, 1148–1151.

  • Ten RM, Blank V, Le Bail O, Kourilsky P and Israel A . (1993). C. R. Acad. Sci. III, 316, 496–501.

  • Williams BR . (1999). Oncogene, 18, 6112–6120.

  • Zhu J, Koken MH, Quignon F, Chelbi-Alix MK, Degos L, Wang ZY, Chen Z and de The H. (1997). Proc. Natl. Acad. Sci. USA, 94, 3978–3983.

Download references

Acknowledgements

We thank Sharon Lynn Salhi and Ian Robbins for editing the manuscript. This work was supported by grants from the Association pour la Recherche contre le Cancer, the Institut National de la Santé et de la Recherche Médicale, the Centre National de la Recherche Scientifique, the Ligue Contre le Cancer Comite's de l'Herault et du Gard, and the Fondation pour la Recherche Me'dicale. LE was funded by Fellowship from Ensemble contre le SIDA

Author information

Authors and Affiliations

  1. CNRS UMR 5160, EFS, 240 avenue Emile Jeanbrau, Montpellier, 34094, Cedex 5, France

    Lucile Espert, Clémence Rey, Laure Gonzalez, Geneviève Degols, Nadir Mechti & Céline Gongora

  2. CNRS UPR 9045, 7, Rue Guy Moquet, Institut André Lwoff, Villejuif, 94801, Cedex, France

    Mounira Kmar Chelbi-Alix

Authors
  1. Lucile Espert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clémence Rey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laure Gonzalez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Geneviève Degols
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mounira Kmar Chelbi-Alix
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nadir Mechti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Céline Gongora
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Nadir Mechti or Céline Gongora.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Espert, L., Rey, C., Gonzalez, L. et al. The exonuclease ISG20 is directly induced by synthetic dsRNA via NF-κB and IRF1 activation. Oncogene 23, 4636–4640 (2004). https://doi.org/10.1038/sj.onc.1207586

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207586

Keywords

This article is cited by

Search

Advanced search

Quick links