The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development

Genes Dev. 2007 Apr 1;21(7):744-9. doi: 10.1101/gad.1519107.

Abstract

Neuronal gene expression is tightly regulated in developing CNS. Here, we demonstrate the anti-neural function of phosphatase SCP1 (small C-terminal domain phosphatase 1) during development. We further show that the neuron-enriched microRNA miR-124 directly targets SCP1-3' untranslated region (UTR) to suppress SCP1 expression. In developing spinal cord, expression of miR-124 and SCP1 is complementary, and miR-124 antagonism phenocopies SCP1 overexpression and vice versa. In P19 cells, miR-124 suppresses SCP1 expression and induces neurogenesis, and SCP1 counteracts this proneural activity of miR-124. Our results suggest that, during CNS development, timely down-regulation of SCP1 is critical for inducing neurogenesis, and miR-124 contributes to this process at least in part by down-regulating SCP1 expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / metabolism
  • Animals
  • Avian Proteins / antagonists & inhibitors
  • Avian Proteins / genetics
  • Avian Proteins / metabolism
  • Base Sequence
  • Cells, Cultured
  • Central Nervous System / embryology*
  • Central Nervous System / enzymology
  • Central Nervous System / metabolism
  • Chick Embryo
  • Chickens
  • Down-Regulation
  • Humans
  • Mice
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Neurons / enzymology
  • Neurons / metabolism*
  • Phosphoprotein Phosphatases / antagonists & inhibitors*
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism
  • Protein Phosphatase 1
  • Repressor Proteins / antagonists & inhibitors*
  • Transcription Factors / antagonists & inhibitors*
  • Transfection

Substances

  • 3' Untranslated Regions
  • Avian Proteins
  • MicroRNAs
  • RE1-silencing transcription factor
  • Repressor Proteins
  • Transcription Factors
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1