Post-transcriptional regulation of FUS and EWS protein expression by miR-141 during neural differentiation

Francesca Svetoni, Elisa De Paola, Piergiorgio La Rosa, Neri Mercatelli, Daniela Caporossi, Claudio Sette*, Maria Paola Paronetto

*Corresponding author

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Brain development involves proliferation, migration and specification of neural progenitor cells, culminating in neuronal circuit formation. Mounting evidence indicates that improper regulation of RNA binding proteins (RBPs), including members of the FET (FUS, EWS, TAF15) family, results in defective cortical development and/or neurodegenerative disorders. However, in spite of their physiological relevance, the precise pattern of FET protein expression in developing neurons is largely unknown. Herein, we found that FUS, EWS and TAF15 expression is differentially regulated during brain development, both in time and in space. In particular, our study identifies a fine-tuned regulation of FUS and EWS during neuronal differentiation, whereas TAF15 appears to be more constitutively expressed. Mechanistically FUS and EWS protein expression is regulated at the post-transcriptional level during neuron differentiation and brain development. Moreover, we identified miR-141 as a key regulator of these FET proteins that modulate their expression levels in differentiating neuronal cells. Thus, our studies uncover a novel link between post-transcriptional regulation of FET proteins expression and neurogenesis.
Original languageEnglish
Pages (from-to)2732-2746
Number of pages15
JournalHuman Molecular Genetics
Volume26
DOIs
Publication statusPublished - 2017

Keywords

  • Animals
  • Brain
  • Cell Differentiation
  • Genetics
  • Genetics (clinical)
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs
  • Molecular Biology
  • Neurogenesis
  • Neurons
  • Protein Processing, Post-Translational
  • RNA Processing, Post-Transcriptional
  • RNA-Binding Protein EWS
  • RNA-Binding Protein FUS
  • RNA-Binding Proteins
  • TATA-Binding Protein Associated Factors

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