Evidence map›Paper›PMID 37328606›Full record

ArticleScientific reports2023

Regulation of microRNA expression by the adaptor protein GRB2.

Amy K Stainthorp, Chi-Chuan Lin, Dapeng Wang, Ragini Medhi, Zamal Ahmed, Kin Man Suen, Eric A Miska, Adrian Whitehouse, John E Ladbury

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

5 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Let-7 Family as a Mediator of Exercise on Alzheimer's Disease.Cellular and molecular neurobiology · 2025
    Review
  3. Review
  4. Review
  5. Review
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

9 authors at 5 institutions in 2 countries.

Amy K StainthorpSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Chi-Chuan LinSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Dapeng WangLeedsOmics, University of Leeds, Leeds, LS2 9JT, UK.
Ragini MedhiWellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
Zamal AhmedDepartment of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Kin Man SuenSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Eric A MiskaWellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
Adrian WhitehouseSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
John E LadburySchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK. j.e.ladbury@leeds.ac.uk.
University of Leeds · GBThe Gurdon Institute · GBInstitute of Structural and Molecular Biology · GBThe University of Texas MD Anderson Cancer Center · USUniversity of Oxford · GB

Funding

Cancer Research UK 22356Cancer Research UK C57233/A22356
6 · The paper itself

Abstract

Protein interactions with the microRNA (miRNA)-mediated gene silencing protein Argonaute 2 (AGO2) control miRNA expression. miRNA biogenesis starts with the production of precursor transcripts and culminates with the loading of mature miRNA onto AGO2 by DICER1. Here we reveal an additional component to the regulatory mechanism for miRNA biogenesis involving the adaptor protein, growth factor receptor-bound protein 2 (GRB2). The N-terminal SH3 domain of GRB2 is recruited to the PAZ domain of AGO2 forming a ternary complex containing GRB2, AGO2 and DICER1. Using small-RNA sequencing we identified two groups of miRNAs which are regulated by the binding of GRB2. First, mature and precursor transcripts of mir-17~92 and mir-221 miRNAs are enhanced. Second, mature, but not precursor, let-7 family miRNAs are diminished suggesting that GRB2 directly affects loading of these miRNAs. Notably, the resulting loss of let-7 augments expression of oncogenic targets such as RAS. Thus, a new role for GRB2 is established with implications for cancer pathogenesis through regulation of miRNA biogenesis and oncogene expression.

Indexed as

MicroRNAsArgonaute ProteinsBase SequenceGene SilencingGRB2 Adaptor ProteinArgonaute ProteinsGRB2 Adaptor ProteinMicroRNAs

Identifiers

PMID37328606
PMCPMC10276003
OpenAlexW4380986951

What OpenQuestion holds

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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.