Evidence map›Paper›PMID 36803582›Full record

ArticleGenome biology2023

Not1 and Not4 inversely determine mRNA solubility that sets the dynamics of co-translational events.

George Allen, Benjamin Weiss, Olesya O Panasenko, Susanne Huch, Zoltan Villanyi, Benjamin Albert, Daniel Dilg, Marina Zagatti, Paul Schaughency, Susan E Liao and 6 more

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

12 citing papers in PubMed, 15 citations in OpenAlex.

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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

16 authors at 4 institutions in 8 countries.

George Allen *Departement of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Benjamin Weiss *Departement of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Olesya O PanasenkoDepartement of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland.ORCID 0000-0002-0990-7472
Susanne HuchSciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
Zoltan VillanyiDepartement of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Benjamin AlbertDepartment of Molecular and Cellular Biology, Faculty of Sciences, Institute of Genetics and Genomics Geneva, University of Geneva, Geneva, Switzerland.
Daniel DilgDepartment of Molecular and Cellular Biology, Faculty of Sciences, Institute of Genetics and Genomics Geneva, University of Geneva, Geneva, Switzerland.
Marina ZagattiDepartement of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Paul SchaughencyDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Susan E LiaoDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-8380-7824
Jeff CordenDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Christine PolteDepartement of Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany.
David ShoreDepartment of Molecular and Cellular Biology, Faculty of Sciences, Institute of Genetics and Genomics Geneva, University of Geneva, Geneva, Switzerland.ORCID 0000-0002-9859-143X
Zoya IgnatovaDepartement of Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany.ORCID 0000-0002-9478-8825
Vicent PelechanoSciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
Martine A CollartDepartement of Microbiology and Molecular Medicine, Institute of Genetics and Genomics Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland. martine.collart@unige.ch.ORCID 0000-0001-6955-1773
University of Geneva · CHJohns Hopkins University · USScience for Life Laboratory · SEUniversität Hamburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe Ccr4-Not complex is mostly known as the major eukaryotic deadenylase. However, several studies have uncovered roles of the complex, in particular of the Not subunits, unrelated to deadenylation and relevant for translation. In particular, the existence of Not condensates that regulate translation elongation dynamics has been reported. Typical studies that evaluate translation efficiency rely on soluble extracts obtained after the disruption of cells and ribosome profiling. Yet cellular mRNAs in condensates can be actively translated and may not be present in such extracts.

resultsIn this work, by analyzing soluble and insoluble mRNA decay intermediates in yeast, we determine that insoluble mRNAs are enriched for ribosomes dwelling at non-optimal codons compared to soluble mRNAs. mRNA decay is higher for soluble RNAs, but the proportion of co-translational degradation relative to the overall mRNA decay is higher for insoluble mRNAs. We show that depletion of Not1 and Not4 inversely impacts mRNA solubilities and, for soluble mRNAs, ribosome dwelling according to codon optimality. Depletion of Not4 solubilizes mRNAs with lower non-optimal codon content and higher expression that are rendered insoluble by Not1 depletion. By contrast, depletion of Not1 solubilizes mitochondrial mRNAs, which are rendered insoluble upon Not4 depletion.

conclusionsOur results reveal that mRNA solubility defines the dynamics of co-translation events and is oppositely regulated by Not1 and Not4, a mechanism that we additionally determine may already be set by Not1 promoter association in the nucleus.

Indexed as

RibosomesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCell Cycle ProteinsCodonProtein BiosynthesisRepressor ProteinsRNA, MessengerRNA StabilitySolubilityTranscription FactorsUbiquitin-Protein LigasesCDC39 protein, S cerevisiaeCell Cycle ProteinsCodonMOT2 protein, S cerevisiaeRepressor ProteinsRNA, MessengerSaccharomyces cerevisiae ProteinsTranscription FactorsUbiquitin-Protein LigasesCodon optimalityCondensationCo-translational mRNA decaymRNA solubilitymRNA stabilityNot1Not4Translation elongation dynamics

Identifiers

PMID36803582
PMCPMC9940351
OpenAlexW4321373817

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.