Evidence map›Paper›PMID 36694129›Full record

ArticleCellular & molecular biology letters2023

Outside the limit: questioning the distance restrictions for cooperative miRNA binding sites.

Caroline Diener, Martin Hart, Claudia Fecher-Trost, Jessica Knittel, Stefanie Rheinheimer, Markus R Meyer, Jens Mayer, Veit Flockerzi, Andreas Keller, Eckart Meese

Abstract readLetter
In one paragraph

Article in Cellular & molecular biology letters, 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
–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

5 citing papers in PubMed.

  1. Article
  2. Article
  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

10 authors.

Caroline DienerInstitute of Human Genetics, Saarland University, 66421, Homburg, Germany. caroline.diener@uni-saarland.de.ORCID http://orcid.org/0000-0002-3222-8419
Martin HartInstitute of Human Genetics, Saarland University, 66421, Homburg, Germany.
Claudia Fecher-TrostDepartment of Experimental and Clinical Pharmacology & Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421, Homburg, Germany.
Jessica KnittelInstitute of Human Genetics, Saarland University, 66421, Homburg, Germany.
Stefanie RheinheimerInstitute of Human Genetics, Saarland University, 66421, Homburg, Germany.
Markus R MeyerDepartment of Experimental and Clinical Toxicology & Pharmacology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421, Homburg, Germany.
Jens MayerInstitute of Human Genetics, Saarland University, 66421, Homburg, Germany.
Veit FlockerziDepartment of Experimental and Clinical Pharmacology & Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421, Homburg, Germany.
Andreas KellerChair for Clinical Bioinformatics, Saarland Informatics Campus, Saarland University, 66123, Saarbrücken, Germany.
Eckart MeeseInstitute of Human Genetics, Saarland University, 66421, Homburg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Among the concepts in biology that are widely taken granted is a potentiated cooperative effect of multiple miRNAs on the same target. This strong hypothesis contrasts insufficient experimental evidence. The quantity as well as the quality of required side constraints of cooperative binding remain largely hidden. For miR-21-5p and miR-155-5p, two commonly investigated regulators across diseases, we selected 15 joint target genes. These were chosen to represent various neighboring 3'UTR binding site constellations, partially exceeding the distance rules that have been established for over a decade. We identified different cooperative scenarios with the binding of one miRNA enhancing the binding effects of the other miRNA and vice versa. Using both, reporter assays and whole proteome analyses, we observed these cooperative miRNA effects for genes that bear 3'UTR binding sites at distances greater than the previously defined limits. Astonishingly, the experiments provide even stronger evidence for cooperative miRNA effects than originally postulated. In the light of these findings the definition of targetomes specified for single miRNAs need to be refined by a concept that acknowledges the cooperative effects of miRNAs.

Indexed as

MicroRNAs3' Untranslated RegionsBinding Sites3' Untranslated RegionsMicroRNAsBinding sitesCooperativityDistancesFunctional interactionsIn silico predictionmicroRNANetworksProteomicsRISCTarget identification

Identifiers

PMID36694129
PMCPMC9875415

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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.