title: Synthesis of two SAPAP3 isoforms from a single mRNA is mediated via alternative translational initiation.
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.
authors: Institute for Human Genetics, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.
authors: John Jia En
authors: JJ
authors: Chua
authors: Claudia
authors: C
authors: Schob
authors: Monika
authors: M
authors: Rehbein
authors: Christos G
authors: CG
authors: Gkogkas
authors: Dietmar
authors: D
authors: Richter
authors: Stefan
authors: S
authors: Kindler
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D018387:Codon, Initiator; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics; D016366:Open Reading Frames; D010442:Peptide Chain Initiation, Translational; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D059368:RNA Isoforms; D051381:Rats; D012377:Rodentia / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D020121:5' Untranslated Regions; D018387:Codon, Initiator; C491275:Dlgap3 protein, rat; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D059368:RNA Isoforms