The eIF4E-Binding Protein 4E-T Is a Component of the mRNA Decay Machinery that Bridges the 5′ and 3′ Termini of Target mRNAs

• Published in: Cell reports (Cambridge) Vol. 11; no. 9; pp. 1425 - 1436
• Main Authors: Nishimura, Tamiko, Padamsi, Zoya, Fakim, Hana, Milette, Simon, Dunham, Wade H., Gingras, Anne-Claude, Fabian, Marc R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.06.2015; Elsevier
• Subjects: HeLa Cells; Humans; Immunoprecipitation; Nucleocytoplasmic Transport Proteins - metabolism; RNA Interference - physiology; RNA Stability - physiology; RNA, Messenger - metabolism; RNA, Small Interfering; Transfection
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.04.065

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. [Display omitted] •4E-T is a component of the mRNA decapping and decay machinery•4E-T promotes the decay of mRNAs targeted by the CCR4-NOT deadenylase complex•4E-T-mediated mRNA decay requires that it bind to eIF4E In this study, Nishimura et al. demonstrate that the human eIF4E-binding protein 4E-T is a component of the mRNA decay machinery. 4E-T promotes the turnover of mRNAs targeted by the CCR4-NOT deadenylase complex.