Evidence map›Paper›PMID 36727461›Full record

ArticleNucleic acids research2023

eIF4A1-dependent mRNAs employ purine-rich 5'UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation.

Tobias Schmidt, Adrianna Dabrowska, Joseph A Waldron, Kelly Hodge, Grigorios Koulouras, Mads Gabrielsen, June Munro, David C Tack, Gemma Harris, Ewan McGhee and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

25 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
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  4. A Dimeric Rocaglate Promotes Multivalent eIF4A-RNA Assembly.bioRxiv : the preprint server for biology · 2026
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  10. Dynamics and Regulation of mRNA Cap Recognition by Human eIF4F.bioRxiv : the preprint server for biology · 2025
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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

17 authors at 5 institutions in 2 countries.

Tobias SchmidtCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.ORCID 0000-0001-7230-1214
Adrianna DabrowskaCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.ORCID 0000-0002-4882-5955
Joseph A WaldronCancer 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.
Grigorios KoulourasCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Mads GabrielsenMVLS Structural Biology and Biophysical Characterisation Facility, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
June MunroCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
David C TackSpectrum Health Office of Research and Education, Spectrum Health System, 15 Michigan Street NE, Grand Rapids, MI 49503, USA.
Gemma HarrisResearch Complex at Harwell, Rutherford Appleton Laboratory, Harwell Campus, Didcot OX11 0FA, UK.
Ewan McGheeCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
David ScottResearch Complex at Harwell, Rutherford Appleton Laboratory, Harwell Campus, Didcot OX11 0FA, UK.ORCID 0000-0002-6726-2078
Leo M CarlinCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Danny HuangCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
John Le QuesneCancer 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.
Ania WilczynskaCancer 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.
Cancer Research UK · GBRutherford Appleton Laboratory · GBSpectrum Health · USUniversity of California, San Francisco · USUniversity of Glasgow · GB

Funding

Cancer Research UK 23983Cancer Research UK 24388Cancer Research UK 29252Cancer Research UK 29256Cancer Research UK 29800Cancer Research UK 30062Medical Research Council MC_UP_A600_1024Medical Research Council MC_UU_00025/6Medical Research Council MR/M01245X/1
6 · The paper itself

Abstract

Altered eIF4A1 activity promotes translation of highly structured, eIF4A1-dependent oncogene mRNAs at root of oncogenic translational programmes. It remains unclear how these mRNAs recruit and activate eIF4A1 unwinding specifically to facilitate their preferential translation. Here, we show that single-stranded RNA sequence motifs specifically activate eIF4A1 unwinding allowing local RNA structural rearrangement and translation of eIF4A1-dependent mRNAs in cells. Our data demonstrate that eIF4A1-dependent mRNAs contain AG-rich motifs within their 5'UTR which specifically activate eIF4A1 unwinding of local RNA structure to facilitate translation. This mode of eIF4A1 regulation is used by mRNAs encoding components of mTORC-signalling and cell cycle progression, and renders these mRNAs particularly sensitive to eIF4A1-inhibition. Mechanistically, we show that binding of eIF4A1 to AG-rich sequences leads to multimerization of eIF4A1 with eIF4A1 subunits performing distinct enzymatic activities. Our structural data suggest that RNA-binding of multimeric eIF4A1 induces conformational changes in the RNA resulting in an optimal positioning of eIF4A1 proximal to the RNA duplex enabling efficient unwinding. Our data proposes a model in which AG-motifs in the 5'UTR of eIF4A1-dependent mRNAs specifically activate eIF4A1, enabling assembly of the helicase-competent multimeric eIF4A1 complex, and positioning these complexes proximal to stable localised RNA structure allowing ribosomal subunit scanning.

Indexed as

Eukaryotic Initiation Factor-4AProtein Biosynthesis5' Untranslated RegionsHumansPurinesRNA, Messenger5' Untranslated RegionsEIF4A1 protein, humanEukaryotic Initiation Factor-4APurinesRNA, Messenger

Identifiers

PMID36727461
PMCPMC9976904
OpenAlexW4318921536

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.