Jafarnejad et al. 2018 (PRJNA421497)

Title	Translational control of ERK signalling pathway by the mRNA cap-binding protein 4EHP
Organism
Number of Samples	4
Release Date	2017/12/07 00:00
Sequencing Types
Protocol Details

GWIPS-viz	Trips-Viz

Title
Authors	Jafarnejad SM,Chapat C,Matta-Camacho E,Gelbart IA,Hesketh GG,Arguello M,Garzia A,Kim SH,Attig J,Shapiro M,Morita M,Khoutorsky A,Alain T,Gkogkas CG,Stern-Ginossar N,Tuschl T,Gingras AC,Duchaine TF,Sonenberg N
Journal	eLife
Publication Date	2018 Feb 7
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 signaling cascade in mammalian cells. © 2018, Jafarnejad et al.
PMC	PMC5819943
PMID	29412140
DOI

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