Wilczynska et al. 2019 (PRJNA556704)

General Details

Title A global overview of translation efficiency and ribosome occupancy at nucleotide resolution in HEK293 cells
Organism
Number of Samples 3
Release Date 2019/07/19 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP216422
ENA SRP216422
GEO GSE134517
BioProject PRJNA556704

Publication

Title
Authors Wilczynska A, Gillen SL, Schmidt T, Meijer HA, Jukes-Jones R, Langlais C, Kopra K, Lu WT, Godfrey JD, Hawley BR, Hodge K, Zanivan S, Cain K, Le Quesne J, Bushell M
Journal Genome biology
Publication Date 2019 Dec 2
Abstract Regulation of the mRNA life cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of action is still not fully understood. Here, we show that eIF4A2 is a major effector of the repressive miRNA pathway functioning via the Ccr4-Not complex. We demonstrate that while DDX6 interacts with Ccr4-Not, its effects in the mechanism are not as pronounced. Through its interaction with the Ccr4-Not complex, eIF4A2 represses mRNAs at translation initiation. We show evidence that native eIF4A2 has similar RNA selectivity to chemically inhibited eIF4A1. eIF4A2 exerts its repressive effect by binding purine-rich motifs which are enriched in the 5'UTR of target mRNAs directly upstream of the AUG start codon. Our data support a model whereby purine motifs towards the 3' end of the 5'UTR are associated with increased ribosome occupancy and possible uORF activation upon eIF4A2 binding.
PMC PMC6886185
PMID 31791371
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR9839460 PRJNA556704 Homo sapiens HEK293 Ribo-Seq Cycloheximide
SRR9839461 PRJNA556704 Homo sapiens HEK293 Ribo-Seq Cycloheximide
SRR9839462 PRJNA556704 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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