KSRP silencing favors neural differentiation of P19 teratocarcinoma cells

Matteo Giovarelli, Gabriele Bucci, Michela Pasero, Roberto Gherzi, Paola Briata

Research output: Contribution to journalArticlepeer-review

Abstract

Understanding the molecular mechanisms that control the balance between multipotency and differentiation is of great importance to elucidate the genesis of both developmental disorders and cell transformation events. To investigate the role of the RNA binding protein KSRP in controlling neural differentiation, we used the P19 embryonal carcinoma cell line that is able to differentiate into neuron-like cells under appropriate culture conditions. We have recently reported that KSRP controls the differentiative fate of multipotent mesenchymal cells owing to its ability to promote decay of unstable transcripts and to favor maturation of selected micro-RNAs (miRNAs) from precursors. Here we report that KSRP silencing in P19 cells favors neural differentiation increasing the expression of neuronal markers. Further, the expression of two master transcriptional regulators of neurogenesis, ASCL1 and JMJD3, was enhanced while the maturation of miR-200 family members from precursors was impaired in KSRP knockdown cells. These molecular changes can contribute to the reshaping of P19 cells transcriptome that follows KSRP silencing. Our data suggests that KSRP function is required to maintain P19 cells in a multipotent undifferentiated state and that its inactivation can orient cells towards neural differentiation.

Original languageEnglish
Pages (from-to)469-479
Number of pages11
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1829
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • MicroRNA maturation
  • MRNA degradation
  • Neural differentiation
  • RNA-binding protein

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Genetics
  • Molecular Biology
  • Structural Biology

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