title: The eIF4E-Binding Protein 4E-T Is a Component of the mRNA Decay Machinery that Bridges the 5' and 3' Termini of Target mRNAs.
abstract: Eukaryotic mRNA degradation often initiates with the recruitment of the CCR4-NOT deadenylase complex and decay factors to the mRNA 3' terminus. How the 3'-proximal decay machinery interacts with the 5'-terminal cap structure in order to engender mRNA decapping and 5'-3' degradation is unclear. Human 4E-T is an eIF4E-binding protein that has been reported to promote mRNA decay, albeit via an unknown mechanism. Here, we show that 4E-T is a component of the mRNA decay machinery and interacts with factors including DDX6, LSM14, and the LSM1-7-PAT1 complex. We also provide evidence that 4E-T associates with, and enhances the decay of, mRNAs targeted by the CCR4-NOT deadenylase complex, including microRNA targets. Importantly, we demonstrate that 4E-T must interact with eIF4E to engender mRNA decay. Taken together, our data support a model where 4E-T promotes mRNA turnover by physically linking the 3'-terminal mRNA decay machinery to the 5' cap via its interaction with eIF4E.
authors.affiliation: Department of Oncology, McGill University, Montreal, QC H3A 0G4, Canada; Segal Cancer Centre, Jewish General Hospital, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada.
authors.forename: Tamiko
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Department of Oncology, McGill University, Montreal, QC H3A 0G4, Canada; Segal Cancer Centre, Jewish General Hospital, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Padamsi
authors.affiliation: Department of Oncology, McGill University, Montreal, QC H3A 0G4, Canada; Segal Cancer Centre, Jewish General Hospital, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada.
authors.forename: Hana
authors.initials: H
authors.lastname: Fakim
authors.affiliation: Department of Oncology, McGill University, Montreal, QC H3A 0G4, Canada; Segal Cancer Centre, Jewish General Hospital, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Milette
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Wade H
authors.initials: WH
authors.lastname: Dunham
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gingras
authors.affiliation: Department of Oncology, McGill University, Montreal, QC H3A 0G4, Canada; Segal Cancer Centre, Jewish General Hospital, Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada. Electronic address: marc.fabian@mcgill.ca.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Fabian
mesh_terms: D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology*; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering; D014162:Transfection
chemical_list: C411571:EIF4ENIF1 protein, human; D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering