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.
Nishimura, T., Padamsi, Z., Fakim, H., Milette, S., Dunham, W. H., Gingras, A. C., & Fabian, M. R. (2015). The eIF4E-Binding Protein 4E-T Is a Component of the mRNA Decay Machinery that Bridges the 5’ and 3’ Termini of Target mRNAs. Cell Reports, 11(9), 1425–1436. https://doi.org/10.1016/j.celrep.2015.04.065