Modulation of SMN nuclear foci and cytoplasmic localization by its C-terminus.
The survival of motor neuron ( SMN1) gene product, SMN, is detected both in the cytoplasm and in nuclear gems and cajal bodies. We show here that SMN exon 6 is essential both for formation of its nuclear foci and for its cytoplasmic localization. However, exon 7 inhibits the formation of SMN nuclear foci but promotes SMN cytoplasmic localization. More interestingly, we find that a random C-terminal tag of five or more amino acids downstream of exon 6 is sufficient to inhibit the occurrence of multiple nuclear foci and to promote cytoplasmic localization of SMNDelta7, the primary product of the SMN2 gene. Moreover, SMNDelta7 proteins that bear spinal muscular atrophy mutations in exon 6 either showed defects in nuclear foci formation or enhanced cytoplasmic localization. We conclude that exon 6 and exon 7 synergistically regulate SMN distribution that may require specific exon 6 motifs but is independent of specific sequences in exon 7.
Hua
Y
Y
Department of Medicine, Program in Neuroscience, University of Massachusetts, Medical School, 364 Plantation Street, LRB 325, Worcester, Massachusetts 01605, USA.
Zhou
J
J
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D020541:Coiled Bodies / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein; D003593:Cytoplasm / Q000378:metabolism*; D005091:Exons; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D017386:Sequence Homology, Amino Acid; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; D049452:Green Fluorescent Proteins