Evidence map›Paper›PMID 27342281›Full record

ArticleNucleic acids research2016

The DDX6-4E-T interaction mediates translational repression and P-body assembly.

Anastasiia Kamenska, Clare Simpson, Caroline Vindry, Helen Broomhead, Marianne Bénard, Michèle Ernoult-Lange, Benjamin P Lee, Lorna W Harries, Dominique Weil, Nancy Standart

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

83 citing papers in PubMed, 131 citations in OpenAlex.

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23 more citing papers are in PubMed but not listed here.

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

10 authors at 4 institutions in 2 countries.

Anastasiia KamenskaDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB21QW, UK.
Clare SimpsonDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB21QW, UK.
Caroline VindryDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB21QW, UK.
Helen BroomheadDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB21QW, UK.
Marianne BénardSorbonne Universités, UPMC, CNRS, IBPS, Developmental Biology Laboratory, 75005 Paris, France.
Michèle Ernoult-LangeSorbonne Universités, UPMC, CNRS, IBPS, Developmental Biology Laboratory, 75005 Paris, France.
Benjamin P LeeInstitute of Biomedical and Clinical Sciences, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW.
Lorna W HarriesInstitute of Biomedical and Clinical Sciences, University of Exeter Medical School, Barrack Road, Exeter EX2 5DW.
Dominique WeilSorbonne Universités, UPMC, CNRS, IBPS, Developmental Biology Laboratory, 75005 Paris, France.
Nancy StandartDepartment of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB21QW, UK nms23@cam.ac.uk.
University of Cambridge · GBCentre National de la Recherche Scientifique · FRUniversity of Exeter · GBSorbonne Université · FR

Funding

Biotechnology and Biological Sciences Research Council BB/J00779X/1
6 · The paper itself

Abstract

4E-Transporter binds eIF4E via its consensus sequence YXXXXLΦ, shared with eIF4G, and is a nucleocytoplasmic shuttling protein found enriched in P-(rocessing) bodies. 4E-T inhibits general protein synthesis by reducing available eIF4E levels. Recently, we showed that 4E-T bound to mRNA however represses its translation in an eIF4E-independent manner, and contributes to silencing of mRNAs targeted by miRNAs. Here, we address further the mechanism of translational repression by 4E-T by first identifying and delineating the interacting sites of its major partners by mass spectrometry and western blotting, including DDX6, UNR, unrip, PAT1B, LSM14A and CNOT4. Furthermore, we document novel binding between 4E-T partners including UNR-CNOT4 and unrip-LSM14A, altogether suggesting 4E-T nucleates a complex network of RNA-binding protein interactions. In functional assays, we demonstrate that joint deletion of two short conserved motifs that bind UNR and DDX6 relieves repression of 4E-T-bound mRNA, in part reliant on the 4E-T-DDX6-CNOT1 axis. We also show that the DDX6-4E-T interaction mediates miRNA-dependent translational repression and de novo P-body assembly, implying that translational repression and formation of new P-bodies are coupled processes. Altogether these findings considerably extend our understanding of the role of 4E-T in gene regulation, important in development and neurogenesis.

Indexed as

Protein BiosynthesisAmino Acid SequenceBinding SitesDEAD-box RNA HelicasesDNA-Binding ProteinsEukaryotic Initiation Factor-4EEukaryotic Initiation Factor-4GGene Expression RegulationHEK293 CellsHeLa CellsHumansNucleocytoplasmic Transport ProteinsProtein BindingProtein Interaction MapsProto-Oncogene ProteinsRNA-Binding ProteinsCNOT1 protein, humanCSDE1 protein, humanDDX6 protein, humanDEAD-box RNA HelicasesDNA-Binding ProteinsEIF4ENIF1 protein, humanEukaryotic Initiation Factor-4EEukaryotic Initiation Factor-4GNucleocytoplasmic Transport ProteinsProto-Oncogene ProteinsRNA-Binding ProteinsRNA, Small InterferingTranscription Factors

Identifiers

PMID27342281
PMCPMC5291280
OpenAlexW2461878290

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.