| First Author | Chapat C | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 21 | Pages | 5425-5430 |
| PubMed ID | 28487484 | Mgi Jnum | J:242290 |
| Mgi Id | MGI:5904882 | Doi | 10.1073/pnas.1701488114 |
| Citation | Chapat C, et al. (2017) Cap-binding protein 4EHP effects translation silencing by microRNAs. Proc Natl Acad Sci U S A 114(21):5425-5430 |
| abstractText | MicroRNAs (miRNAs) play critical roles in a broad variety of biological processes by inhibiting translation initiation and by destabilizing target mRNAs. The CCR4-NOT complex effects miRNA-mediated silencing, at least in part through interactions with 4E-T (eIF4E transporter) protein, but the precise mechanism is unknown. Here we show that the cap-binding eIF4E-homologous protein 4EHP is an integral component of the miRNA-mediated silencing machinery. We demonstrate that the cap-binding activity of 4EHP contributes to the translational silencing by miRNAs through the CCR4-NOT complex. Our results show that 4EHP competes with eIF4E for binding to 4E-T, and this interaction increases the affinity of 4EHP for the cap. We propose a model wherein the 4E-T/4EHP interaction engenders a closed-loop mRNA conformation that blocks translational initiation of miRNA targets. |
