Characterization of a gene encoding survival motor neuron (SMN)-related protein, a constituent of the spliceosome complex

Mutations in the gene encoding the Survival Motor Neuron (SMN) protein areresponsible for autosomal recessive proximal spinal muscular atrophy (SMA).SMN orthologues have been identified in the nematode worm Caenorhabditiselegans and the yeast Schizosaccharomyces pombe but, to date, no humanparalogues have been described. Here we describe identification andcharacterization of an SMN-related protein (SMNrp) gene that encodes anovel protein of 239 amino acids, which has recently been identified as aconstituent of the spliceosome complex and designated SPF30. Significantsimilarity to the SMN protein is apparent only within a central region ofSMNrp that represents a tudor domain. The SMNrp/SPF30 gene has been mappedto chromosome 10q23. It is differentially expressed, with abundant levelsin skeletal muscle. An exclusively nuclear localization for SMNrp incultured cells and muscle sections was revealed using GFP fusion constructsand thereafter confirmed with a polyclonal antibody raised against SMNrp.Overexpression of SMNrp as a fusion protein in HeLa cells in cultureinduced dose-dependent apoptosis with positive TUNEL staining. In additionto a possible role for this protein as a pro-apoptotic factor, SMN and itsrelated protein share significant similarities in sequence and cellularfunction.