title: Nuclear localization of cytoplasmic poly(A)-binding protein upon rotavirus infection involves the interaction of NSP3 with eIF4G and RoXaN.
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.
authors.affiliation: Virologie Moléculaire et Structurale INRA UMR 1157, CNRS UMR 2472, IFR 115, Avenue de la Terrasse, 91198 Gif sur Yvette, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Harb
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Becker
authors.forename: Damien
authors.initials: D
authors.lastname: Vitour
authors.forename: Carolina H
authors.initials: CH
authors.lastname: Baron
authors.forename: Patrice
authors.initials: P
authors.lastname: Vende
authors.forename: Spencer C
authors.initials: SC
authors.lastname: Brown
authors.forename: Susanne
authors.initials: S
authors.lastname: Bolte
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Arold
authors.forename: Didier
authors.initials: D
authors.lastname: Poncet
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism*; D000882:Haplorhini; D006801:Humans; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012401:Rotavirus / Q000502:physiology*; D017384:Sequence Deletion; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
chemical_list: D039603:Eukaryotic Initiation Factor-4G; D050505:Mutant Proteins; C082740:NSP3 protein, Rotavirus; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; D017361:Viral Nonstructural Proteins; C484647:ZC3H7B protein, human
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