Fine-tuning of the PAX-SIX-EYA-DACH network by multiple microRNAs controls embryo myogenesis
| Autor: | Camille Viaut, Andrea Münsterberg |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
PAX3
MiRNA binding Chick Embryo Biology Muscle Development 03 medical and health sciences 0302 clinical medicine In vivo microRNA Gene expression Animals Luciferase Muscle Skeletal 3' Untranslated Regions PAX3 Transcription Factor Molecular Biology Transcription factor 030304 developmental biology Homeodomain Proteins 0303 health sciences Gene knockdown Myogenesis Gene Expression Regulation Developmental Embryo Cell Biology Cell biology MicroRNAs Somites 030217 neurology & neurosurgery Transcription Factors Developmental Biology |
| Zdroj: | Developmental Biology. 469:68-79 |
| ISSN: | 0012-1606 |
| Popis: | MicroRNAs (miRNAs), short non-coding RNAs, which act post-transcriptionally to regulate gene expression, are of widespread significance during development and disease, including muscle disease. Advances in sequencing technology and bioinformatics led to the identification of a large number of miRNAs in vertebrates and other species, however, for many of these miRNAs specific roles have not yet been determined. LNAin situhybridisation has revealed expression patterns of somite-enriched miRNAs, here we focus on characterising the functions of miR-128. We show that antagomir-mediated knock-down (KD) of miR-128 in developing chick somites has a negative impact on skeletal myogenesis. Computational analysis identified the transcription factorEYA4as a candidate target consistent with the observation that miR-128 andEYA4display similar expression profiles. Luciferase assays confirmed that miR-128 interacts with theEYA43’UTR. Furthermore,in vivoexperiments suggest thatEYA4is regulated by miR-128, asEYA4expression is derepressed after antagomir-mediated inhibition of miR-128. EYA4 is a member of the PAX-SIX-EYA-DACH (PSED) network of transcription factors. Therefore, we identified additional candidate miRNA binding sites in the 3’UTR ofSIX1/4, EYA1/2/3andDACH1. Using the miRanda algorithm, we found sites for miR-128, as well as for other myogenic miRNAs, miR-1a, miR-206 and miR-133a, some of these were experimentally confirmed as functional miRNA-target sites. Our results reveal that miR-128 is involved in regulating skeletal myogenesis by targetingEYA4transcripts and moreover that the PSED network of transcription factors is co-regulated by multiple muscle-enriched microRNAs. |
| Databáze: | OpenAIRE |
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