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Marek’s disease virus microRNA designated Mdv1-pre-miR-M4 targets both cellular and viral genes

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Abstract

Mdv1-miR-M4 is one of 25 microRNAs (miRNAs) expressed by Marek’s disease virus (MDV-1), an oncogenic alphaherpesvirus that induces fatal T-cell lymphoma in chickens. Mdv1-miR-M4 was shown to be the second functional viral ortholog of miR-155, a cellular miRNA that plays a crucial role in several physiological and pathological processes in lymphocyte biology. In this study, we investigated a panel of putative mdv1-miR-M4 targets involved in gene networks affecting both cellular and viral life cycles. Using luciferase reporter assays, we showed that mdv1-miR-M4-5P and miR-155 efficiently targeted a common set of 3′ untranslated regions (3′UTR) of six cellular genes (GPM6B, RREB1, c-Myb, MAP3K7IP2, PU.1 and C/EBP). In addition, we also investigated the interactions between mdv1-miR-M4-5P and mdv1-miR-M43P and viral mRNAs encoding UL28 and UL32 in both reporter and western blot assays. Mdv1-miR-M4 specifically inhibited the translation of these two viral proteins, which are involved in the cleavage/packaging of herpesvirus DNA.

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Acknowledgments

We thank Sébastien Pfeffer (IBMP, Strasbourg) for his advice concerning northern blots and small RNA cloning experiments and Sylvie Laurent for her advice concerning western blots. We thank Dr. Nair Venugopal (IAH, Compton) for providing the infectious BAC clone p-RB1B. Benoît Muylkens is a postdoctoral research fellow supported by the Fonds National de la Recherche Scientifique (FNRS). This work was supported by the Ligue Nationale contre le cancer, Comité du Cher, AIP P0258 of the Institut National de la Recherche Agronomique and the Agence Nationale de la Recherche (ANR-07-MIME-012-01).

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Authors and Affiliations

  1. Transcription, Lymphome Viro-Induit, University François Rabelais, UFR Sciences et Techniques, Avenue Monge, 37200, Tours, France

    Benoît Muylkens, Damien Coupeau, Ginette Dambrine, Sascha Trapp & Denis Rasschaert

  2. Department of Animal Health INRA, Nouzilly, France

    Ginette Dambrine

  3. Embryology, Veterinary Department, Faculty of Sciences, University of Namur, FUNDP, 5000, Namur, Belgium

    Benoît Muylkens

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  1. Benoît Muylkens
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  2. Damien Coupeau
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  3. Ginette Dambrine
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  5. Denis Rasschaert
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Correspondence to Denis Rasschaert.

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B. Muylkens and D. Coupeau contributed equally to this study.

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705_2010_777_MOESM1_ESM.eps

Fig. S1 (A) Alignment of mdv1-miR-M4-5P and chicken cellular targets. (B) Alignment of gga-miR-155 and chicken cellular targets. (C) Alignment of mdv1-miR-M4-5P, mdv1-miR-M4-3P or gga-miR-155 and viral targets Supplementary material 1 (EPS 308 kb)

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Muylkens, B., Coupeau, D., Dambrine, G. et al. Marek’s disease virus microRNA designated Mdv1-pre-miR-M4 targets both cellular and viral genes. Arch Virol 155, 1823–1837 (2010). https://doi.org/10.1007/s00705-010-0777-y

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