Translational control of ERK signaling through miRNA/4EHP-directed silencing
- McGill University, Canada
- Weizmann Institute of Science, Israel
- Lunenfeld-Tanenbaum Research Institute, Canada
- The Rockefeller University, United States
- The Francis Crick Institute, United Kingdom
- University of Ottawa, Canada
- University of Edinburgh, United Kingdom
Abstract
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 signalling cascade in mammalian cells.
Data availability
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Translational control of ERK signalling pathway by the mRNA cap-binding protein 4EHPPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE107826).
Article and author information
Author details
Noam Stern-Ginossar
Funding
Canadian Institutes of Health Research (FDN-148423)
- Nahum Sonenberg
Fonds de la Recherche en Sante du Quebec
- Thomas F Duchaine
Natural Sciences and Engineering Research Council of Canada (RGPIN-2014-06434)
- Anne-Claude Gingras
Canadian Institutes of Health Research (FDN-143301)
- Anne-Claude Gingras
Canadian Institutes of Health Research (MOP-123352)
- Thomas F Duchaine
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Jafarnejad et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Translational control of ERK signaling through miRNA/4EHP-directed silencing
eLife 7:e35034.
https://doi.org/10.7554/eLife.35034
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