Park et al. 2017 (PRJNA381596)

General Details

Title mTORC1 balances cellular amino acid supply with demand for protein synthesis through post-transcriptional control of ATF4
Organism
Number of Samples 4
Release Date 2017/04/04 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP103009
ENA SRP103009
GEO 0.0
BioProject PRJNA381596

Publication

Title
Authors Park Y, Reyna-Neyra A, Philippe L, Thoreen CC
Journal Cell reports
Publication Date 2017 May 9
Abstract The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that is commonly deregulated in human diseases. Here we find that mTORC1 controls a transcriptional program encoding amino acid transporters and metabolic enzymes through a mechanism also used to regulate protein synthesis. Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element recognized by activating transcription factor 4 (ATF4), a key effector of the integrated stress response. ATF4 translation is normally induced by the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) through a mechanism that requires upstream open reading frames (uORFs) in the ATF4 5' UTR. mTORC1 also controls ATF4 translation through uORFs, but independently of changes in eIF2α phosphorylation. mTORC1 instead employs the 4E-binding protein (4E-BP) family of translation repressors. These results link mTORC1-regulated demand for protein synthesis with an ATF4-regulated transcriptional program that controls the supply of amino acids to the translation machinery. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
PMC PMC5811220
PMID 28494858
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR5413155 PRJNA381596 Homo sapiens HEK293 Ribo-Seq Cycloheximide
SRR5413156 PRJNA381596 Homo sapiens HEK293 Ribo-Seq Cycloheximide
SRR5413157 PRJNA381596 Homo sapiens HEK293 Ribo-Seq Cycloheximide
SRR5413158 PRJNA381596 Homo sapiens HEK293 Ribo-Seq Cycloheximide
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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