Evidence map›Paper›PMID 34615539›Full record

ArticleGenome biology2021

Differential regulation of mRNA fate by the human Ccr4-Not complex is driven by coding sequence composition and mRNA localization.

Sarah L Gillen, Chiara Giacomelli, Kelly Hodge, Sara Zanivan, Martin Bushell, Ania Wilczynska

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Designing 5' UTR sequences improves the capacity of mRNA therapeutics in preclinical models of aging and obesity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Sarah L GillenCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.
Chiara GiacomelliCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.
Kelly HodgeCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.
Sara ZanivanCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK.
Martin BushellCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK. martin.bushell@glasgow.ac.uk.
Ania WilczynskaCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK. awilcz@gmail.com.ORCID 0000-0003-4548-9367
Cancer Research UK · GBCancer Research UK Scotland Institute · GB

Funding

Biotechnology and Biological Sciences Research Council BB/M001865/1Biotechnology and Biological Sciences Research Council BB/N017005/1Cancer Research UK 24388Cancer Research UK 29252Cancer Research UK 29800Cancer Research UK A29252Cancer Research UK A31287Cancer Research UK C596/A17196Medical Research Council MC_EX_G0902052Medical Research Council MC_UP_A600_1024
6 · The paper itself

Abstract

backgroundRegulation 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.

resultsThis 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.

conclusionsWe 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.

Indexed as

Gene Expression RegulationProtein BiosynthesisRNA StabilityCodonGene Knockdown TechniquesHumansNuclear ProteinsRibosomesRNA, MessengerTranscription FactorsCNOT1 protein, humanCodonNuclear ProteinsRNA, MessengerTranscription Factors

Identifiers

PMID34615539
PMCPMC8496106
OpenAlexW3203884779

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.