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

  1. Jaya Visvanathan1,
  2. Seunghee Lee2,
  3. Bora Lee2,
  4. Jae W. Lee2,4, and
  5. Soo-Kyung Lee1,2,3,5,6,7
  1. 1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA;
  2. 2 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA;
  3. 3 Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA;
  4. 4 Department of Medicine- Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, Texas 77030, USA;
  5. 5 The Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA;
  6. 6 Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA

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.

Keywords

Footnotes

| Table of Contents

Life Science Alliance