Evidence map›Paper›PMID 33300035›Full record

ArticleNucleic acids research2021

MiR-CLIP reveals iso-miR selective regulation in the miR-124 targetome.

Yuluan Wang, Charlotte Soneson, Anna L Malinowska, Artur Laski, Souvik Ghosh, Alexander Kanitz, Luca F R Gebert, Mark D Robinson, Jonathan Hall

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 33% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. The MicroRNA Family Gets Wider: The IsomiRs Classification and Role.Frontiers in cell and developmental biology · 2021
    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 4 institutions in 2 countries.

Yuluan WangInstitute of Pharmaceutical Sciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
Charlotte SonesonDepartment of Molecular Life Sciences and SIB Swiss Institute of Bioinformatics, University of Zurich, 8057, Zurich, Switzerland.
Anna L MalinowskaInstitute of Pharmaceutical Sciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
Artur LaskiInstitute of Pharmaceutical Sciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
Souvik GhoshBiozentrum, University of Basel, 4056 Basel, Switzerland.
Alexander KanitzBiozentrum, University of Basel, 4056 Basel, Switzerland.
Luca F R GebertDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Mark D RobinsonDepartment of Molecular Life Sciences and SIB Swiss Institute of Bioinformatics, University of Zurich, 8057, Zurich, Switzerland.
Jonathan HallInstitute of Pharmaceutical Sciences, ETH Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
ETH Zurich · CHSIB Swiss Institute of Bioinformatics · CHUniversity of Basel · CHScripps Research Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many microRNAs regulate gene expression via atypical mechanisms, which are difficult to discern using native cross-linking methods. To ascertain the scope of non-canonical miRNA targeting, methods are needed that identify all targets of a given miRNA. We designed a new class of miR-CLIP probe, whereby psoralen is conjugated to the 3p arm of a pre-microRNA to capture targetomes of miR-124 and miR-132 in HEK293T cells. Processing of pre-miR-124 yields miR-124 and a 5'-extended isoform, iso-miR-124. Using miR-CLIP, we identified overlapping targetomes from both isoforms. From a set of 16 targets, 13 were differently inhibited at mRNA/protein levels by the isoforms. Moreover, delivery of pre-miR-124 into cells repressed these targets more strongly than individual treatments with miR-124 and iso-miR-124, suggesting that isomirs from one pre-miRNA may function synergistically. By mining the miR-CLIP targetome, we identified nine G-bulged target-sites that are regulated at the protein level by miR-124 but not isomiR-124. Using structural data, we propose a model involving AGO2 helix-7 that suggests why only miR-124 can engage these sites. In summary, access to the miR-124 targetome via miR-CLIP revealed for the first time how heterogeneous processing of miRNAs combined with non-canonical targeting mechanisms expand the regulatory range of a miRNA.

Indexed as

Gene Expression RegulationModels, Genetic3' Untranslated RegionsAmino Acid MotifsArgonaute ProteinsBase SequenceBinding SitesBiotinCross-Linking ReagentsDNA, ComplementaryGTP-Binding ProteinsHEK293 CellsHumansImmunoprecipitationMicroRNAsNuclear Proteins3' Untranslated RegionsAGO2 protein, humanArgonaute ProteinsBiotinCross-Linking ReagentsDNA, ComplementaryGNL3L protein, humanGTP-Binding ProteinsMicroRNAsMIRN1243 microRNA, humanMIRN124 microRNA, humanMIRN132 microRNA, humanNuclear ProteinsStreptavidinTrioxsalen

Identifiers

PMID33300035
PMCPMC7797034
OpenAlexW3111411728

What OpenQuestion holds

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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.