Synthesis of two SAPAP3 isoforms from a single mRNA is mediated via alternative translational initiation

John Jia En Chua, Claudia Schob, Monika Rehbein, Christos G Gkogkas, Dietmar Richter, Stefan Kindler

Research output: Contribution to journalArticlepeer-review

Abstract

In mammalian neurons, targeting and translation of specific mRNAs in dendrites contribute to synaptic plasticity. After nuclear export, mRNAs designated for dendritic transport are generally assumed to be translationally dormant and activity of individual synapses may locally trigger their extrasomatic translation. We show that the long, GC-rich 5'-untranslated region of dendritic SAPAP3 mRNA restricts translation initiation via a mechanism that involves an upstream open reading frame (uORF). In addition, the uORF enables the use of an alternative translation start site, permitting synthesis of two SAPAP3 isoforms from a single mRNA. While both isoforms progressively accumulate at postsynaptic densities during early rat brain development, their levels relative to each other vary in different adult rat brain areas. Thus, alternative translation initiation events appear to regulate relative expression of distinct SAPAP3 isoforms in different brain regions, which may function to influence synaptic plasticity.
Original languageEnglish
Pages (from-to)484
JournalScientific Reports
Volume2
DOIs
Publication statusPublished - 2012

Keywords

  • 5' Untranslated Regions
  • Animals
  • Base Sequence
  • Brain
  • Cell Line, Tumor
  • Codon, Initiator
  • Gene Expression Regulation
  • Humans
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins
  • Neuronal Plasticity
  • Open Reading Frames
  • Peptide Chain Initiation, Translational
  • Protein Biosynthesis
  • Protein Isoforms
  • RNA Isoforms
  • Rats
  • Rodentia
  • Sequence Alignment

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