A eutherian-specific microRNA controls the translation of Satb2 in a model of cortical differentiation

Manuella Martins, Silvia Galfrè, Marco Terrigno, Luca Pandolfini, Irene Appolloni, Keagan Dunville, Andrea Marranci, Milena Rizzo, Alberto Mercatanti, Laura Poliseno, Francesco Morandin, Marco Pietrosanto, Manuela Helmer-Citterich, Paolo Malatesta, Robert Vignali, Federico Cremisi

Research output: Contribution to journalArticlepeer-review

Abstract

Cerebral cortical development is controlled by key transcription factors that specify the neuronal identities in the different layers. The mechanisms controlling their expression in distinct cells are only partially known. We investigated the expression and stability of Tbr1, Bcl11b, Fezf2, Satb2, and Cux1 mRNAs in single developing mouse cortical cells. We observe that Satb2 mRNA appears much earlier than its protein and in a set of cells broader than expected, suggesting an initial inhibition of its translation, subsequently released during development. Mechanistically, Satb2 3′UTR modulates protein translation of GFP reporters during mouse corticogenesis. We select miR-541, a eutherian-specific miRNA, and miR-92a/b as the best candidates responsible for SATB2 inhibition, being strongly expressed in early and reduced in late progenitor cells. Their inactivation triggers robust and premature SATB2 translation in both mouse and human cortical cells. Our findings indicate RNA interference as a major mechanism in timing cortical cell identities.

Original languageEnglish
Pages (from-to)1496-1509
Number of pages14
JournalStem Cell Reports
Volume16
Issue number6
DOIs
Publication statusPublished - Jun 8 2021

Keywords

  • cell fate
  • cell identity
  • corpus callosum
  • cortex
  • cortical layering
  • developmental timing
  • in vitro corticogenesis
  • mammalian evolution
  • microRNA
  • miR-catch
  • neural stem cells
  • post-transcriptional control
  • SATB2

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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