| Literature DB >> 28487484 |
Clément Chapat1,2, Seyed Mehdi Jafarnejad1,2, Edna Matta-Camacho1,2, Geoffrey G Hesketh3, Idit A Gelbart4, Jan Attig5, Christos G Gkogkas6, Tommy Alain7, Noam Stern-Ginossar4, Marc R Fabian8, Anne-Claude Gingras3,9, Thomas F Duchaine10,2, Nahum Sonenberg10,2.
Abstract
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.Entities:
Keywords: 4E-T; 4EHP; CCR4–NOT; mRNA translation; microRNA
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Year: 2017 PMID： 28487484 PMCID： PMC5448183 DOI： 10.1073/pnas.1701488114
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205