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Virus-Cell Interactions

Nuclear Localization of Cytoplasmic Poly(A)-Binding Protein upon Rotavirus Infection Involves the Interaction of NSP3 with eIF4G and RoXaN

Maya Harb, Michelle M. Becker, Damien Vitour, Carolina H. Baron, Patrice Vende, Spencer C. Brown, Susanne Bolte, Stefan T. Arold, Didier Poncet
Maya Harb
1Virologie Moléculaire et Structurale INRA UMR 1157, CNRS UMR 2472, IFR 115, Avenue de la Terrasse, 91198 Gif sur Yvette, France
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Michelle M. Becker
1Virologie Moléculaire et Structurale INRA UMR 1157, CNRS UMR 2472, IFR 115, Avenue de la Terrasse, 91198 Gif sur Yvette, France
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Damien Vitour
1Virologie Moléculaire et Structurale INRA UMR 1157, CNRS UMR 2472, IFR 115, Avenue de la Terrasse, 91198 Gif sur Yvette, France
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Carolina H. Baron
1Virologie Moléculaire et Structurale INRA UMR 1157, CNRS UMR 2472, IFR 115, Avenue de la Terrasse, 91198 Gif sur Yvette, France
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Patrice Vende
1Virologie Moléculaire et Structurale INRA UMR 1157, CNRS UMR 2472, IFR 115, Avenue de la Terrasse, 91198 Gif sur Yvette, France
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Spencer C. Brown
2Institut des Sciences du Végétal, UPR CNRS 2355, IFR 87, 91198 Gif-sur-Yvette Cedex, France
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Susanne Bolte
2Institut des Sciences du Végétal, UPR CNRS 2355, IFR 87, 91198 Gif-sur-Yvette Cedex, France
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Stefan T. Arold
3Centre de Biochimie Structurale, INSERM UMR 554, CNRS UMR 5048, 34090 Montpellier Cedex, France
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Didier Poncet
1Virologie Moléculaire et Structurale INRA UMR 1157, CNRS UMR 2472, IFR 115, Avenue de la Terrasse, 91198 Gif sur Yvette, France
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  • For correspondence: poncet@vms.cnrs-gif.fr
DOI: 10.1128/JVI.00872-08
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ABSTRACT

Rotavirus nonstructural protein NSP3 interacts specifically with the 3′ end of viral mRNAs, with the eukaryotic translation initiation factor eIF4G, and with RoXaN, a cellular protein of yet-unknown function. By evicting cytoplasmic poly(A) binding protein (PABP-C1) from translation initiation complexes, NSP3 shuts off the translation of cellular polyadenylated mRNAs. We show here that PABP-C1 evicted from eIF4G by NSP3 accumulates in the nucleus of rotavirus-infected cells. Through modeling of the NSP3-RoXaN complex, we have identified mutations in NSP3 predicted to interrupt its interaction with RoXaN without disturbing the NSP3 interaction with eIF4G. Using these NSP3 mutants and a deletion mutant unable to associate with eIF4G, we show that the nuclear localization of PABP-C1 not only is dependent on the capacity of NSP3 to interact with eIF4G but also requires the interaction of NSP3 with a specific region in RoXaN, the leucine- and aspartic acid-rich (LD) domain. Furthermore, we show that the RoXaN LD domain functions as a nuclear export signal and that RoXaN tethers PABP-C1 with RNA. This work identifies RoXaN as a cellular partner of NSP3 involved in the nucleocytoplasmic localization of PABP-C1.

  • Copyright © 2008 American Society for Microbiology
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Nuclear Localization of Cytoplasmic Poly(A)-Binding Protein upon Rotavirus Infection Involves the Interaction of NSP3 with eIF4G and RoXaN
Maya Harb, Michelle M. Becker, Damien Vitour, Carolina H. Baron, Patrice Vende, Spencer C. Brown, Susanne Bolte, Stefan T. Arold, Didier Poncet
Journal of Virology Oct 2008, 82 (22) 11283-11293; DOI: 10.1128/JVI.00872-08

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Nuclear Localization of Cytoplasmic Poly(A)-Binding Protein upon Rotavirus Infection Involves the Interaction of NSP3 with eIF4G and RoXaN
Maya Harb, Michelle M. Becker, Damien Vitour, Carolina H. Baron, Patrice Vende, Spencer C. Brown, Susanne Bolte, Stefan T. Arold, Didier Poncet
Journal of Virology Oct 2008, 82 (22) 11283-11293; DOI: 10.1128/JVI.00872-08
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KEYWORDS

Eukaryotic Initiation Factor-4G
Poly(A)-Binding Proteins
Protein Interaction Mapping
RNA-binding proteins
rotavirus
viral nonstructural proteins

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