title: Overexpressed human survival motor neurone isoforms, SMNDeltaexon7 and SMN+exon7, both form intranuclear gems but differ in cytoplasmic distribution.
abstract: Homozygous mutations of the telomeric survival motor neurone gene (SMN1) cause spinal muscular atrophy (SMA). The centromeric copy gene (SMN2) generally skips exon 7 during splicing and fails to compensate for SMN1 deficits, so SMA cells have reduced SMN protein and few nuclear gems. To investigate the role of exon 7 in SMN localisation, cDNAs for full-length SMN and SMNDeltaexon 7 were overexpressed in COS cells, neurones and SMA fibroblasts. Both constructs formed discrete intranuclear bodies colocalising with p80-coilin, but produced more cytoplasmic aggregates in cells overexpressing exon 7. Hence, the exon 7 domain enhances SMN aggregation but is not critical for gem formation.
authors.affiliation: Division of Medical and Molecular Genetics, GKT School of Medicine, Guy's Hospital, London SE1 9RT, UK.
authors.forename: E
authors.initials: E
authors.lastname: Dodds
authors.forename: M G
authors.initials: MG
authors.lastname: Dunckley
authors.forename: R G
authors.initials: RG
authors.lastname: Roberts
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
authors.forename: C E
authors.initials: CE
authors.lastname: Shaw
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein; D003593:Cytoplasm / Q000378:metabolism* / Q000648:ultrastructure; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology; D016601:RNA-Binding Proteins; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; D014162:Transfection
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; C526473:Smn1 protein, rat; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; C068921:p80-coilin