title: Mutations in the survival motor neuron (SMN) protein alter the dynamic nature of nuclear bodies.
abstract: The childhood disorder spinal muscular atrophy (SMA) is caused by reduced expression of the survival motor neuron (SMN) protein. SMN is a multifunctional protein that has been implicated in the production, processing and transport of RNA and ribonucleoproteins (RNPs). Within the nucleus, SMN is predominantly targeted to Cajal bodies (CB), which are involved in the maturation and processing of several subclasses of RNPs. Here, we show that the SMN exon 2b-encoded domain (SMN2b) is independently sufficient to mediate CB targeting, but that the resulting bodies are less dynamic than those containing full-length SMN protein. We also show that while two SMN proteins harbouring SMA-causing point mutations (A2G and S262I) are efficiently targeted to CBs, they also display reduced nuclear movement.
authors.affiliation: Clinical Neurobiology, Institute of Biomedical and Clinical Sciences, Peninsula Medical School, University of Exeter, Heavitree Rd, Exeter, EX1 2LU, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Morse
authors.forename: Adrian G
authors.initials: AG
authors.lastname: Todd
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Shaw
authors.forename: Alison L
authors.initials: AL
authors.lastname: McConville
authors.forename: Iain M
authors.initials: IM
authors.lastname: Robinson
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Young
mesh_terms: D002648:Child; D020541:Coiled Bodies / Q000378:metabolism*; D005091:Exons; D006367:HeLa Cells; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D055532:SMN Complex Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D010455:Peptides; D011993:Recombinant Fusion Proteins; D055532:SMN Complex Proteins