EMBO Rep.: co-auth.: group Gatfield

EMBO Rep. 2022 Jul 28;e54762. doi: 10.15252/embr.202254762. 

Global and precise identification of functional miRNA targets in mESCs by integrative analysis

Moritz Schaefer # 1 2Amena Nabih # 1 2Daniel Spies 1 2Victoria Hermes 1Maxime Bodak 1 2Harry Wischnewski 1Patrick Stalder 1 2Richard Patryk Ngondo 1Luz Angelica Liechti 3Tatjana Sajic 4Ruedi Aebersold 4David Gatfield 3Constance Ciaudo 1


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.

Keywords: Tfap4; integrative analysis; miR-290-295 cluster; microRNA; mouse embryonic stem cells.