Translational control of ERK signaling through miRNA/4EHP-directed silencing

Seyed Mehdi Jafarnejad, Clément Chapat, Edna Matta-Camacho, Idit Anna Gelbart, Geoffrey G. Hesketh, Meztli Arguello, Aitor Garzia, Sung Hoon Kim, Jan Attig, Maayan Shapiro, Masahiro Morita, Arkady Khoutorsky, Tommy Alain, G. Gkogkas Christos, Noam Stern-Ginossar, Thomas Tuschl, Anne Claude Gingras, Thomas F. Duchaine, Nahum Sonenberg

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


MicroRNAs (miRNAs) exert a broad influence over gene expression by directing effector activities that impinge on translation and stability of mRNAs. We recently discovered that the cap-binding protein 4EHP is a key component of the mammalian miRNA-Induced Silencing Complex (miRISC), which mediates gene silencing. However, little is known about the mRNA repertoire that is controlled by the 4EHP/miRNA mechanism or its biological importance. Here, using ribosome profiling, we identify a subset of mRNAs that are translationally controlled by 4EHP. We show that the Dusp6 mRNA, which encodes an ERK1/2 phosphatase, is translationally repressed by 4EHP and a specific miRNA, miR-145. This promotes ERK1/2 phosphorylation, resulting in augmented cell growth and reduced apoptosis. Our findings thus empirically define the integral role of translational repression in miRNA-induced gene silencing and reveal a critical function for this process in the control of the ERK signaling cascade in mammalian cells.

Original languageEnglish (US)
Article numbere35034
StatePublished - Feb 7 2018

ASJC Scopus subject areas

  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience


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