The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development.
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.
Visvanathan
Jaya
J
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Lee
Seunghee
S
Lee
Bora
B
Lee
Jae W
JW
Lee
Soo-Kyung
SK
D020413:3' Untranslated Regions / Q000378:metabolism; D000818:Animals; D030161:Avian Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D002490:Central Nervous System / Q000196:embryology* / Q000201:enzymology / Q000378:metabolism; D002642:Chick Embryo; D002645:Chickens; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D054645:Protein Phosphatase 1; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D014162:Transfection; D000099229:RE1-Silencing Transcription Factor
D020413:3' Untranslated Regions; D030161:Avian Proteins; D035683:MicroRNAs; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor