ArticleNucleic acids research2024
Looking for a needle in a haystack: de novo phenotypic target identification reveals Hippo pathway-mediated miR-202 regulation of egg production.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Circulating microRNAs reveal egg-brain crosstalk and a brain-predominant microRNA linked to the onset of the next reproductive cycle in iteroparous salmonids.BMC biology · 2026Article
- Dynamic interplay of maternal and paternal contributions to offspring phenotype in Eurasian perch.BMC biology · 2026Article
- Derepression of a single microRNA target causes female infertility in mice.Nucleic acids research · 2026Article
- Nuclear Argonaute:miRNA complexes recognize target sequences within chromatin-associated RNA and silence gene expression.Nucleic acids research · 2025Article
- Parent-of-origin regulation by maternal auts2 shapes neurodevelopment and behavior in fish.Genome biology · 2025Article
- Exploring the Fanconi Anemia Gene Expression and Regulation by MicroRNAs in Gilthead Seabream (Sparus aurata) at Different Gonadal Development Stages.Marine biotechnology (New York, N.Y.) · 2025Article
- Differentially expressed miRNAs offer new perspective into cave adaptation of Astyanax mexicanus.Annals of the New York Academy of Sciences · 2025Article
- CRISPR-based dissection of miRNA binding sites using isogenic cell lines is hampered by pervasive noise.Nucleic acids research · 2025Article
- A new perspective on microRNA-guided gene regulation specificity, and its potential generalization to transcription factors and RNA-binding proteins.Nucleic acids research · 2024Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Understanding microRNA (miRNA) functions has been hampered by major difficulties in identifying their biological target(s). Currently, the main limitation is the lack of a suitable strategy to identify biologically relevant targets among a high number of putative targets. Here we provide a proof of concept of successful de novo (i.e. without prior knowledge of its identity) miRNA phenotypic target (i.e. target whose de-repression contributes to the phenotypic outcomes) identification from RNA-seq data. Using the medaka mir-202 knock-out (KO) model in which inactivation leads to a major organism-level reproductive phenotype, including reduced egg production, we introduced novel criteria including limited fold-change in KO and low interindividual variability in gene expression to reduce the list of 2853 putative targets to a short list of 5. We selected tead3b, a member of the evolutionarily-conserved Hippo pathway, known to regulate ovarian functions, due to its remarkably strong and evolutionarily conserved binding affinity for miR-202-5p. Deleting the miR-202-5p binding site in the 3' UTR of tead3b, but not of other Hippo pathway members sav1 and vgll4b, triggered a reduced egg production phenotype. This is one of the few successful examples of de novo functional assignment of a miRNA phenotypic target in vivo in vertebrates.
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Registered trials
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.