TY - JOUR
T1 - Translational control of ERK signaling through miRNA/4EHP-directed silencing
AU - Jafarnejad, Seyed Mehdi
AU - Chapat, Clément
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
N1 - Publisher Copyright:
© Jafarnejad et al.
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.
UR - https://www.scopus.com/pages/publications/85043528495
UR - https://www.scopus.com/pages/publications/85043528495#tab=citedBy
U2 - 10.7554/eLife.35034
DO - 10.7554/eLife.35034
M3 - Article
C2 - 29412140
AN - SCOPUS:85043528495
SN - 2050-084X
VL - 7
JO - eLife
JF - eLife
M1 - e35034
ER -