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

Seyed Mehdi Jafarnejad; Clement 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

doi:10.7554/eLife.35034

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

Seyed Mehdi Jafarnejad, Clement 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

Department of Molecular Genetics

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	35034
Number of pages	18
Journal	eLife
Volume	7
DOIs	https://doi.org/10.7554/eLife.35034
State	Published - 7 Feb 2018

All Science Journal Classification (ASJC) codes

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

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10.7554/eLife.35034

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Jafarnejad, S. M., Chapat, C., Matta-Camacho, E., Gelbart, I. A., Hesketh, G. G., Arguello, M., Garzia, A., Kim, S.-H., Attig, J., Shapiro, M., Morita, M., Khoutorsky, A., Alain, T., Christos, G. G., Stern-Ginossar, N., Tuschl, T., Gingras, A.-C., Duchaine, T. F., & Sonenberg, N. (2018). Translational control of ERK signaling through miRNA/4EHP-directed silencing. eLife, 7, Article 35034. https://doi.org/10.7554/eLife.35034

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title = "Translational control of ERK signaling through miRNA/4EHP-directed silencing",

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.",

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

note = "Publisher Copyright: {\textcopyright} Jafarnejad et al.",

year = "2018",

month = feb,

day = "7",

doi = "10.7554/eLife.35034",

language = "الإنجليزيّة",

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journal = "eLife",

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Jafarnejad, SM, Chapat, C, Matta-Camacho, E, Gelbart, IA, Hesketh, GG, Arguello, M, Garzia, A, Kim, S-H, Attig, J, Shapiro, M, Morita, M, Khoutorsky, A, Alain, T, Christos, GG, Stern-Ginossar, N, Tuschl, T, Gingras, A-C, Duchaine, TF & Sonenberg, N 2018, 'Translational control of ERK signaling through miRNA/4EHP-directed silencing', eLife, vol. 7, 35034. https://doi.org/10.7554/eLife.35034

TY - JOUR

T1 - Translational control of ERK signaling through miRNA/4EHP-directed silencing

AU - Jafarnejad, Seyed Mehdi

AU - Chapat, Clement

AU - Matta-Camacho, Edna

AU - Gelbart, Idit Anna

AU - Hesketh, Geoffrey G.

AU - Arguello, Meztli

AU - Garzia, Aitor

AU - Kim, Sung-Hoon

AU - Attig, Jan

AU - Shapiro, Maayan

AU - Morita, Masahiro

AU - Khoutorsky, Arkady

AU - Alain, Tommy

AU - Christos, G. Gkogkas

AU - Stern-Ginossar, Noam

AU - Tuschl, Thomas

AU - Gingras, Anne-Claude

AU - Duchaine, Thomas F.

AU - Sonenberg, Nahum

PY - 2018/2/7

Y1 - 2018/2/7

N2 - 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.

AB - 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.

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U2 - 10.7554/eLife.35034

DO - 10.7554/eLife.35034

M3 - مقالة

SN - 2050-084X

VL - 7

JO - eLife

JF - eLife

M1 - 35034

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

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