title: Alternative polyadenylation and differential expression of Shank mRNAs in the synaptic neuropil.
abstract: The stability and dynamics of synapses rely on tight regulation of the synaptic proteome. Shank proteins, encoded by the three genes Shank1, Shank2 and Shank3 are scaffold molecules in the postsynaptic density of excitatory neurons that contribute to activity-dependent neuronal signalling. Mutations in the Shank genes are associated with neurological diseases. Using state-of-the-art technologies, we investigated the levels of expression of the Shank family messenger RNAs (mRNAs) within the synaptic neuropil of the rat hippocampus. We detected all three Shank transcripts in the neuropil of CA1 pyramidal neurons. We found Shank1 to be the most abundantly expressed among the three Shank mRNA homologues. We also examined the turnover of Shank mRNAs and predict the half-lives of Shank1, Shank2 and Shank3 mRNAs to be 18-28 h. Using 3'-end sequencing, we identified novel 3' ends for the Shank1 and Shank2 3' untranslated regions (3' UTRs) that may contribute to the diversity of alternative polyadenylation (APA) for the Shank transcripts. Our findings consolidate the view that the Shank molecules play a central role at the postsynaptic density. This study may shed light on synaptopathologies associated with disruption of local protein synthesis, perhaps linked to mutations in mRNA 3' UTRs or inappropriate 3' end processing.
authors.affiliation: Max Planck Institute for Brain Research, , Max-von-Laue Strasse 4, Frankfurt am Main 60438, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Epstein
authors.forename: Georgi
authors.initials: G
authors.lastname: Tushev
authors.forename: Tristan J
authors.initials: TJ
authors.lastname: Will
authors.forename: Irena
authors.initials: I
authors.lastname: Vlatkovic
authors.forename: Iván J
authors.initials: IJ
authors.lastname: Cajigas
authors.forename: Erin M
authors.initials: EM
authors.lastname: Schuman
mesh_terms: D000818:Animals; D001483:Base Sequence; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006207:Half-Life; D015151:Immunoblotting; D017403:In Situ Hybridization; D042282:Microdissection; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019581:Neuropil / Q000378:metabolism*; D026723:Polyadenylation; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013569:Synapses / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C120531:Shank1 protein, rat
keywords: 3′ untranslated region; Shank mRNA; alternative polyadenylation; hippocampus; synaptic neuropil