Mutations in the Survival Motor Neuron (SMN) Protein Alter the Dynamic Nature of Nuclear Bodies

• Published in: Neuromolecular medicine 2011-03, Vol.13 (1), p.77-87
• Main Authors: Morse, Robert, Todd, Adrian G., Shaw, Debra J., McConville, Alison L., Robinson, Iain M., Young, Philip J.
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Child; Coiled Bodies - metabolism; Exons; HeLa Cells; Humans; Internal Medicine; Muscular Atrophy, Spinal - genetics; Muscular Atrophy, Spinal - metabolism; Mutation; Neurology; Neurosciences; Original Paper; Peptides - genetics; Peptides - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; SMN Complex Proteins - genetics; SMN Complex Proteins - metabolism
• ISSN: 1535-1084; 1559-1174
• DOI: 10.1007/s12017-010-8139-1

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.