The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development (original) (raw)
- Jaya Visvanathan1,
- Seunghee Lee2,
- Bora Lee2,
- Jae W. Lee2,4, and
- Soo-Kyung Lee1,2,3,5,6,7
- 1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA;
- 2 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA;
- 3 Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA;
- 4 Department of Medicine- Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, Texas 77030, USA;
- 5 The Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA;
- 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.
Footnotes
↵7 Corresponding author.
↵7 E-MAIL sklee{at}bcm.edu; FAX (713) 790-0545.Supplemental material is available at http://www.genesdev.org.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1519107
- Received November 30, 2006.
- Accepted February 15, 2007.
Copyright © 2007, Cold Spring Harbor Laboratory Press