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

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Zheng, Sika ; Gray, Erin E ; Chawla, Geetanjali ; Porse, Bo Torben ; O'Dell, Thomas J ; Black, Douglas L. / PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. In: Nature Neuroscience. 2012 ; Vol. 15, No. 3. pp. 381-8, S1.

Bibtex

@article{3b5adeb95473432780768464fa15b4f0,
title = "PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2",
abstract = "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.",
keywords = "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",
author = "Sika Zheng and Gray, {Erin E} and Geetanjali Chawla and Porse, {Bo Torben} and O'Dell, {Thomas J} and Black, {Douglas L}",
year = "2012",
doi = "10.1038/nn.3026",
language = "English",
volume = "15",
pages = "381--8, S1",
journal = "Reviews in the Neurosciences",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "3",

}

RIS

TY - JOUR

T1 - PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2

AU - Zheng, Sika

AU - Gray, Erin E

AU - Chawla, Geetanjali

AU - Porse, Bo Torben

AU - O'Dell, Thomas J

AU - Black, Douglas L

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Age Factors

KW - Animals

KW - Carrier Proteins

KW - Cell Differentiation

KW - Cells, Cultured

KW - Cerebral Cortex

KW - Dendrites

KW - Electric Stimulation

KW - Electrophoretic Mobility Shift Assay

KW - Embryo, Mammalian

KW - Excitatory Postsynaptic Potentials

KW - Exons

KW - Gene Expression Regulation, Developmental

KW - Green Fluorescent Proteins

KW - Guanylate Kinase

KW - Hippocampus

KW - Homeodomain Proteins

KW - Membrane Proteins

KW - Mice

KW - Mice, Transgenic

KW - Neural Stem Cells

KW - Neuroblastoma

KW - Neurogenesis

KW - Neurons

KW - Patch-Clamp Techniques

KW - Polypyrimidine Tract-Binding Protein

KW - RNA Isoforms

KW - RNA Splicing

KW - RNA, Messenger

KW - RNA, Small Interfering

KW - Transcription Factors

KW - Transfection

U2 - 10.1038/nn.3026

DO - 10.1038/nn.3026

M3 - Journal article

VL - 15

SP - 381-8, S1

JO - Reviews in the Neurosciences

JF - Reviews in the Neurosciences

SN - 1097-6256

IS - 3

ER -

ID: 36840443