Nuclear Localization of Cytoplasmic Poly(A)-Binding Protein upon Rotavirus Infection Involves the Interaction of NSP3 with eIF4G and RoXaN
Copyright policy )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.
- The University of Texas System United States
- French Institute of Health and Medical Research France
- Département Sciences sociales, agriculture et alimentation, espace et environnement France
- Vanderbilt University United States
- Institut Pasteur France
Rotavirus, PAXILLIN LD MOTIFS, Viral Nonstructural Proteins, MESH: Poly(A)-Binding Proteins, MESH: Mutant Proteins, Protein Interaction Mapping, Site-Directed, MESH: Animals, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, MESH: Haplorhini, MESH: Mutagenesis, Sequence Deletion, RNA-Binding Proteins, MESH: Rotavirus, MESH: Eukaryotic Initiation Factor-4G, Haplorhini, MESH: Sequence Deletion, MESH: Amino Acid Substitution, Protein Transport, POLY(A) BINDING-PROTEIN, MESSENGER-RNA, Protein Binding, MESH: Protein Transport, 570, ENDOPLASMIC-RETICULUM, REVERSE GENETICS SYSTEM, Poly(A)-Binding Proteins, Cell Line, CAP-POLY(A) SYNERGY, MESH: Protein Binding, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Animals, Humans, Protein Interaction Domains and Motifs, MESH: Protein Interaction Domains and Motifs, MESH: Humans, Binding Sites, MESH: Protein Interaction Mapping, STRESS GRANULES, ADHESION TARGETING DOMAIN, MESH: Cell Line, MESH: RNA-Binding Proteins, MESH: Binding Sites, Amino Acid Substitution, Mutagenesis, Site-Directed, MESH: Viral Nonstructural Proteins, TRANSLATION INITIATION-FACTOR, Mutant Proteins, Eukaryotic Initiation Factor-4G
Rotavirus, PAXILLIN LD MOTIFS, Viral Nonstructural Proteins, MESH: Poly(A)-Binding Proteins, MESH: Mutant Proteins, Protein Interaction Mapping, Site-Directed, MESH: Animals, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, MESH: Haplorhini, MESH: Mutagenesis, Sequence Deletion, RNA-Binding Proteins, MESH: Rotavirus, MESH: Eukaryotic Initiation Factor-4G, Haplorhini, MESH: Sequence Deletion, MESH: Amino Acid Substitution, Protein Transport, POLY(A) BINDING-PROTEIN, MESSENGER-RNA, Protein Binding, MESH: Protein Transport, 570, ENDOPLASMIC-RETICULUM, REVERSE GENETICS SYSTEM, Poly(A)-Binding Proteins, Cell Line, CAP-POLY(A) SYNERGY, MESH: Protein Binding, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Animals, Humans, Protein Interaction Domains and Motifs, MESH: Protein Interaction Domains and Motifs, MESH: Humans, Binding Sites, MESH: Protein Interaction Mapping, STRESS GRANULES, ADHESION TARGETING DOMAIN, MESH: Cell Line, MESH: RNA-Binding Proteins, MESH: Binding Sites, Amino Acid Substitution, Mutagenesis, Site-Directed, MESH: Viral Nonstructural Proteins, TRANSLATION INITIATION-FACTOR, Mutant Proteins, Eukaryotic Initiation Factor-4G
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