Evidence map›Paper›PMID 42490457›Full record

ArticleScience advances2026

The AGO2 adaptor LIMD1 expands the functional and evolutionary reach of microRNA targeting.

Alex F F Crozier, Kunal M Shah, Paul Grevitt, Anisha Thind, Eleni Maniati, Jun Wang, Kylie Shen, Diana Cox, Vinothini Rajeeve, Pedro Cutillas and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. ClonalLife science alliance · 2026
    Article
  2. Article
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

15 authors.

Alex F F CrozierCentre for Cancer Cell and Molecular Biology, Barts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0000-0001-8719-5426
Kunal M ShahCentre for Cancer Cell and Molecular Biology, Barts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0000-0002-4508-9606
Paul GrevittCentre for Cancer Cell and Molecular Biology, Barts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0000-0001-8224-1315
Anisha ThindCentre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0009-0000-8881-4428
Eleni ManiatiCentre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0000-0001-6993-9890
Jun WangCentre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0000-0003-2509-9599
Kylie ShenEclipse BioInnovations, San Diego, CA, USA.ORCID 0000-0002-1554-0777
Diana CoxEclipse BioInnovations, San Diego, CA, USA.
Vinothini RajeeveCell Signalling and Proteomics Laboratory, Centre for Cancer Evolution, Barts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0000-0002-6361-4291
Pedro CutillasCell Signalling and Proteomics Laboratory, Centre for Cancer Evolution, Barts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0000-0002-3426-2274
Dimitris LagosYork Biomedical Research Institute, University of York, York, UK.ORCID 0000-0003-0637-281X
Faraz MardakhehDepartment of Biochemistry, University of Oxford, South Parks Road, Oxford, UK.ORCID 0000-0003-3896-0827
Sam Griffiths-JonesSchool of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.ORCID 0000-0001-6043-807X
Antonio MarcoSchool of Life Sciences, University of Essex, Colchester, UK.ORCID 0000-0002-8603-7503
Tyson V SharpCentre for Cancer Cell and Molecular Biology, Barts Cancer Institute, Queen Mary University of London, London, UK.ORCID 0000-0003-1861-7984

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MicroRNA (miRNA) silencing is classically ascribed to RNA-sequence rules that guide Argonaute 2 (AGO2) targeting. Using chimeric eCLIP and complementary analyses in CRISPR-edited human lung epithelial cells, we show that efficient miRNA targeting also depends on the AGO2 adaptor-scaffold LIMD1. In LIMD1-deficient cells, AGO2 binds more miRNAs, but each AGO2-miRNA engages fewer transcripts and sites, reducing occupancy and halving both the breadth and depth of targeting. LIMD1 dependence is most pronounced for poorly conserved, weakly seed-paired sites that nonetheless form stable duplexes. LIMD1 deficiency alters AGO2 footprints and derepresses oncogenic targets inversely correlated with LIMD1 expression in lung adenocarcinoma. Thus, LIMD1 modifies the outcome of sequence-defined interactions that would otherwise be infrequent, unstable, or unproductive, revealing an adaptor-governed layer of posttranscriptional regulation beyond RNA-sequence rules.

Indexed as

Argonaute ProteinsEvolution, MolecularIntracellular Signaling Peptides and ProteinsLIM Domain ProteinsMicroRNAsHumansAGO2 protein, humanArgonaute ProteinsIntracellular Signaling Peptides and ProteinsLIMD1 protein, humanLIM Domain ProteinsMicroRNAs

Identifiers

PMID42490457
PMCPMC13394485

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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.