title: Developmental attenuation of N-methyl-D-aspartate receptor subunit expression by microRNAs.
abstract: BACKGROUND
  N-methyl-D-aspartate receptors (NMDARs) are a subtype of ionotropic glutamate receptors and are expressed throughout the central nervous system (CNS). Their activity is required for excitatory synaptic transmission, the developmental refinement of neural circuits and for the expression of many forms of synaptic plasticity. NMDARs are obligate heterotetramers and the expression of their constituent subunits is developmentally and anatomically regulated. In rodent cortex and hippocampus, the GluN2B subunit is expressed at high levels early in development and decreases to plateau levels later while expression of the GluN2A subunit has a concomitant increase. Regulation of GluN2A and GluN2B expressions are incompletely understood. Here, we showed the influence of miRNAs in this process.
  
  
  RESULTS
  Two miRNAs, miR-19a and miR-539 can influence the levels of NMDARs subunits, as they target the mRNAs encoding GluN2A and GluN2B respectively. MiR-539 also modified the expression of the transcription factor REST, a known regulator of NMDAR subunit expression.
  
  
  CONCLUSIONS
  miR-19a and miR-539, in collaboration with REST, serve to set the levels of GluN2A and GluN2B precisely during development. These miRNAs offer an entry point for interventions that affect plasticity and a novel approach to treat neurodegenerative diseases.
authors.affiliation: Neuroscience Research Institute, Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA. caroline.corbel@gmail.com.|Present address: EA4250-Laboratoire d'Ingénierie des Matériaux de Bretagne, Equipe Génie des Bioprocédés et Biomolécules, Université de Bretagne Sud, CER Yves Coppens, Vannes, 56017, France. caroline.corbel@gmail.com.
authors.forename: Caroline
authors.initials: C
authors.lastname: Corbel
authors.affiliation: Neuroscience Research Institute, Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA. israel.hernandez@lifesci.ucsb.edu.
authors.forename: Israel
authors.initials: I
authors.lastname: Hernandez
authors.affiliation: Neuroscience Research Institute, Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA. wubian500@gmail.com.
authors.forename: Bian
authors.initials: B
authors.lastname: Wu
authors.affiliation: Neuroscience Research Institute, Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA. kenneth.kosik@lifesci.ucsb.edu.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kosik
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D055495:Neurogenesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D016194:Receptors, N-Methyl-D-Aspartate; C586754:MIRN19 microRNA, rat; C121001:NR2B NMDA receptor