Weiss et al. 2021 (PRJNA704316)

General Details

Title Analysis of the eIF4E3-dependent translatome after Torin1-induced stress in N2a cells ctrl and eIF4E3 KO
Organism
Number of Samples 12
Release Date 2021/02/23 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP307718
ENA SRP307718
GEO
BioProject PRJNA704316

Publication

Title
Authors Weiss B,Allen GE,Kloehn J,Abid K,Jaquier-Gubler P,Curran JA
Journal Nucleic acids research
Publication Date 2021 May 21
Abstract The eIF4E are a family of initiation factors that bind the mRNA 5' cap, regulating the proteome and the cellular phenotype. eIF4E1 mediates global translation and its activity is controlled via the PI3K/AKT/mTOR pathway. mTOR down-regulation results in eIF4E1 sequestration into an inactive complex with the 4E binding proteins (4EBPs). The second member, eIF4E2, regulates the translatome during hypoxia. However, the exact function of the third member, eIF4E3, has remained elusive. We have dissected its function using a range of techniques. Starting from the observation that it does not interact with 4EBP1, we demonstrate that eIF4E3 recruitment into an eIF4F complex occurs when Torin1 inhibits the mTOR pathway. Ribo-seq studies demonstrate that this complex (eIF4FS) is translationally active during stress and that it selects specific mRNA populations based on 5' TL (UTR) length. The interactome reveals that it associates with cellular proteins beyond the cognate initiation factors, suggesting that it may have 'moon-lighting' functions. Finally, we provide evidence that cellular metabolism is altered in an eIF4E3 KO background but only upon Torin1 treatment. We propose that eIF4E3 acts as a second branch of the integrated stress response, re-programming the translatome to promote 'stress resistance' and adaptation. © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
PMC PMC8136781
PMID 33893802
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR13769802 PRJNA704316 Mus musculus Neuro2a Ribo-Seq
SRR13769803 PRJNA704316 Mus musculus Neuro2a Ribo-Seq
SRR13769804 PRJNA704316 Mus musculus Neuro2a Ribo-Seq
SRR13769805 PRJNA704316 Mus musculus Neuro2a Ribo-Seq
SRR13769806 PRJNA704316 Mus musculus Neuro2a Ribo-Seq
SRR13769807 PRJNA704316 Mus musculus Neuro2a Ribo-Seq
SRR13769808 PRJNA704316 Mus musculus Neuro2a Ribo-Seq
SRR13769809 PRJNA704316 Mus musculus Neuro2a Ribo-Seq
SRR13769810 PRJNA704316 Mus musculus Neuro2a Ribo-Seq
SRR13769811 PRJNA704316 Mus musculus Neuro2a Ribo-Seq
SRR13769812 PRJNA704316 Mus musculus Neuro2a Ribo-Seq
SRR13769813 PRJNA704316 Mus musculus Neuro2a Ribo-Seq
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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