Spinal muscular atrophy disrupts the interaction of ZPR1 with the SMN protein.
The survival motor neurons (smn) gene in mice is essential for embryonic viability. In humans, mutation of the telomeric copy of the SMN1 gene causes spinal muscular atrophy, an autosomal recessive disease. Here we report that the SMN protein interacts with the zinc-finger protein ZPR1 and that these proteins colocalize in small subnuclear structures, including gems and Cajal bodies. SMN and ZPR1 redistribute from the cytoplasm to the nucleus in response to serum. This process is disrupted in cells from patients with Werdnig-Hoffman syndrome (spinal muscular atrophy type I) that have SMN1 mutations. Similarly, decreased ZPR1 expression prevents SMN localization to nuclear bodies. Our data show that ZPR1 is required for the localization of SMN in nuclear bodies.
Gangwani
L
L
Program in Molecular Medicine, University of Massachussetts Medical School, 373 Plantation St, Worcester, Massachussetts 01605, USA.
Mikrut
M
M
Theroux
S
S
Sharma
M
M
Davis
R J
RJ
D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D026901:Membrane Transport Proteins; D009134:Muscular Atrophy, Spinal / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D016335:Zinc Fingers
D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526472:Smn1 protein, mouse; D055533:Survival of Motor Neuron 1 Protein; C099746:ZPR1 protein, human