Wu et al. 2020 (PRJNA593553)

General Details

Title ZAK activation on colliding ribosomes triggers SAPK signaling pathways to regulate cell fate
Organism
Number of Samples 4
Release Date 2019/12/04 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP234715
ENA SRP234715
GEO
BioProject PRJNA593553

Publication

Title
Authors Wu CC,Peterson A,Zinshteyn B,Regot S,Green R
Journal Cell
Publication Date 2020 Jul 23
Abstract Problems arising during translation of mRNAs lead to ribosome stalling and collisions that trigger a series of quality control events. However, the global cellular response to ribosome collisions has not been explored. Here, we uncover a function for ribosome collisions in signal transduction. Using translation elongation inhibitors and general cellular stress conditions, including amino acid starvation and UV irradiation, we show that ribosome collisions activate the stress-activated protein kinase (SAPK) and GCN2-mediated stress response pathways. We show that the MAPKKK ZAK functions as the sentinel for ribosome collisions and is required for immediate early activation of both SAPK (p38/JNK) and GCN2 signaling pathways. Selective ribosome profiling and biochemistry demonstrate that although ZAK generally associates with elongating ribosomes on polysomal mRNAs, it specifically auto-phosphorylates on the minimal unit of colliding ribosomes, the disome. Together, these results provide molecular insights into how perturbation of translational homeostasis regulates cell fate. Copyright © 2020 Elsevier Inc. All rights reserved.
PMC PMC7384957
PMID 32610081
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR11569080 PRJNA593553 Homo sapiens Ribo-Seq untreated
SRR11569081 PRJNA593553 Homo sapiens Ribo-Seq untreated
SRR11569082 PRJNA593553 Homo sapiens Ribo-Seq
SRR11569083 PRJNA593553 Homo sapiens 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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