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PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2

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  • Sika Zheng
  • Erin E Gray
  • Geetanjali Chawla
  • Bo Torben Porse
  • Thomas J O'Dell
  • Douglas L Black
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Postsynaptic density protein 95 (PSD-95) is essential for synaptic maturation and plasticity. Although its synaptic regulation has been widely studied, the control of PSD-95 cellular expression is not understood. We found that Psd-95 was controlled post-transcriptionally during neural development. Psd-95 was transcribed early in mouse embryonic brain, but most of its product transcripts were degraded. The polypyrimidine tract binding proteins PTBP1 and PTBP2 repressed Psd-95 (also known as Dlg4) exon 18 splicing, leading to premature translation termination and nonsense-mediated mRNA decay. The loss of first PTBP1 and then of PTBP2 during embryonic development allowed splicing of exon 18 and expression of PSD-95 late in neuronal maturation. Re-expression of PTBP1 or PTBP2 in differentiated neurons inhibited PSD-95 expression and impaired the development of glutamatergic synapses. Thus, expression of PSD-95 during early neural development is controlled at the RNA level by two PTB proteins whose sequential downregulation is necessary for synapse maturation.
Original languageEnglish
JournalNature Neuroscience
Volume15
Issue number3
Pages (from-to)381-8, S1
ISSN1097-6256
DOIs
Publication statusPublished - 2012

    Research areas

  • Age Factors, Animals, Carrier Proteins, Cell Differentiation, Cells, Cultured, Cerebral Cortex, Dendrites, Electric Stimulation, Electrophoretic Mobility Shift Assay, Embryo, Mammalian, Excitatory Postsynaptic Potentials, Exons, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Guanylate Kinase, Hippocampus, Homeodomain Proteins, Membrane Proteins, Mice, Mice, Transgenic, Neural Stem Cells, Neuroblastoma, Neurogenesis, Neurons, Patch-Clamp Techniques, Polypyrimidine Tract-Binding Protein, RNA Isoforms, RNA Splicing, RNA, Messenger, RNA, Small Interfering, Transcription Factors, Transfection

ID: 36840443