National Center of Competence
in Research, RNA & Disease

Functional miRNAs in mESCs Identified

The Ciaudo lab in collaboration with the Gatfield and Aebersold labs applied an integrative approach to determine which transcripts in mouse Embryonic Stem Cells are regulated directly by miRNAs and found that less than 10% are, opposite to previous approaches that estimated that up to 60% are. Furthermore, their analyses found TFAP4 to be an important transcription factor for early development and their integrative approach could be applied to other systems and the datasets generated used to generate better models for prediciting functional miRNA-mRNA interactions. Their results have been published in the article "Global and precise identification of functional miRNA targets in mESCs by integrative analysis " in EMBO Reports.

Synopsis
Integrative analysis of transcriptome data from miRNA-depleted mESC lines, miRNA interaction predictions and AGO-binding profiles allows for the identification of direct and functional miRNA targets. These data support the development of algorithms to predict functional miRNA-mRNA interactions.

  • Less than 10% of transcribed genes in mESCs show evidence for direct and functional regulation by miRNAs.
  • TFAP4 is regulated by miRNAs in mESCs and plays an important role in the regulation of gene expression.
  • Depletion of Tfap4 in Drosha_KO mESCs is not sufficient to rescue global miRNA phenotypes.

Abstract
MicroRNA (miRNA) loaded Argonaute (AGO) complexes regulate gene expression via direct base pairing with their mRNA targets. Previous works suggest that up to 60% of mammalian transcripts might be subject to miRNA-mediated regulation, but it remains largely unknown which fraction of these interactions are functional in a specific cellular context. Here, we integrate transcriptome data from a set of miRNA-depleted mouse embryonic stem cell (mESC) lines with published miRNA interaction predictions and AGO-binding profiles. Using this integrative approach, combined with molecular validation data, we present evidence that < 10% of expressed genes are functionally and directly regulated by miRNAs in mESCs. In addition, analyses of the stem cell-specific miR-290-295 cluster target genes identify TFAP4 as an important transcription factor for early development. The extensive datasets developed in this study will support the development of improved predictive models for miRNA-mRNA functional interactions.

Read the Publication in EMBO Reports (Open Access)

Abstract, figure, synopsis and title from Schaefer, Nabih et al (2022) EMBO Rep published under a CC BY-NC-ND 4.0 license.

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