Spinal muscular atrophy disrupts the interaction of ZPR1 with the SMN protein

The survival motor neurons (smn) gene in mice is essential for embryonic vi ability. In humans, mutation of the telomeric copy of the SMN1 gene causes spinal muscular atrophy, an autosomal recessive disease. Here we report tha t the SMN protein interacts with the zinc-finger protein ZPR1 and that thes e proteins colocalize in small subnuclear structures, including gems and Ca jal bodies. SMN and ZPR1 redistribute from the cytoplasm to the nucleus in response to serum. This process is disrupted in cells from patients with We rdnig-Hoffman syndrome (spinal muscular atrophy type I) that have SMN1 muta tions. Similarly, decreased ZPR1 expression prevents SMN localization to nu clear bodies. Our data show that ZPR1 is required for the localization of S MN in nuclear bodies.