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

• 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

SummaryEukaryotic 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.

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