Gillen et al. 2021 (PRJNA664116)

General Details

Title Ribosome Profiling with CNOT1 depletion
Organism
Number of Samples 6
Release Date 2020/09/17 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP282906
ENA SRP282906
GEO GSE158141
BioProject PRJNA664116

Publication

Title
Authors Gillen SL,Giacomelli C,Hodge K,Zanivan S,Bushell M,Wilczynska A
Journal Genome biology
Publication Date 2021 Oct 6
Abstract Regulation of protein output at the level of translation allows for a rapid adaptation to dynamic changes to the cell's requirements. This precise control of gene expression is achieved by complex and interlinked biochemical processes that modulate both the protein synthesis rate and stability of each individual mRNA. A major factor coordinating this regulation is the Ccr4-Not complex. Despite playing a role in most stages of the mRNA life cycle, no attempt has been made to take a global integrated view of how the Ccr4-Not complex affects gene expression. This study has taken a comprehensive approach to investigate post-transcriptional regulation mediated by the Ccr4-Not complex assessing steady-state mRNA levels, ribosome position, mRNA stability, and protein production transcriptome-wide. Depletion of the scaffold protein CNOT1 results in a global upregulation of mRNA stability and the preferential stabilization of mRNAs enriched for G/C-ending codons. We also uncover that mRNAs targeted to the ER for their translation have reduced translational efficiency when CNOT1 is depleted, specifically downstream of the signal sequence cleavage site. In contrast, translationally upregulated mRNAs are normally localized in p-bodies, contain disorder-promoting amino acids, and encode nuclear localized proteins. Finally, we identify ribosome pause sites that are resolved or induced by the depletion of CNOT1. We define the key mRNA features that determine how the human Ccr4-Not complex differentially regulates mRNA fate and protein synthesis through a mechanism linked to codon composition, amino acid usage, and mRNA localization. © 2021. The Author(s).
PMC PMC8496106
PMID 34615539
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR12660872 PRJNA664116 Homo sapiens HEK293 Ribo-Seq Cycloheximide
SRR12660873 PRJNA664116 Homo sapiens HEK293 Ribo-Seq Cycloheximide
SRR12660874 PRJNA664116 Homo sapiens HEK293 Ribo-Seq Cycloheximide
SRR12660880 PRJNA664116 Homo sapiens HEK293 Ribo-Seq Cycloheximide
SRR12660881 PRJNA664116 Homo sapiens HEK293 Ribo-Seq Cycloheximide
SRR12660882 PRJNA664116 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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