Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Genome-wide association study implicates CHRNA2 in cannabis use disorder

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. The ASXL1-G643W variant accelerates the development of CEBPA mutant acute myeloid leukemia

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Myelodysplastic syndrome patient-derived xenografts: from no options to many

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. ERG Controls B Cell Development by Promoting Igh V-to-DJ Recombination

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Heterozygous loss of Srp72 in mice is not associated with major hematological phenotypes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Sika Zheng
  • Erin E Gray
  • Geetanjali Chawla
  • Bo Torben Porse
  • Thomas J O'Dell
  • Douglas L Black
Vis graf over relationer
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