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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.
OriginalsprogEngelsk
TidsskriftNature Neuroscience
Vol/bind15
Udgave nummer3
Sider (fra-til)381-8, S1
ISSN1097-6256
DOI
StatusUdgivet - 2012

ID: 36840443