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 are responsible for autosomal recessive proximal spinal muscular atrophy (SMA). SMN orthologues have been identified in the nematode worm Caenorhabditis e legans and the yeast Schizo-saccharomyces pombe but, to date, no human para logues have been described. Here we describe identification and characteriz ation of an SMN-related protein (SMNrp) gene that encodes a novel protein o f 239 amino acids, which has recently been identified as; a constituent of the spliceosome complex and designated SPF30, Significant similarity to the SMN protein is apparent only within a central region of SMNrp that represe nts a tudor domain, The SMNrp/SPF30 gene has been mapped to chromosome 10q2 3, It is; differentially expressed, with abundant levels in skeletal muscle , An exclusively nuclear localization for SMNrp in cultured cells and muscl e sections was revealed using GFP fusion constructs and thereafter confirme d with a polyclonal antibody raised against SMNrp, Overexpression of SMNrp as a fusion protein in HeLa cells in culture induced dose-dependent apoptos is with positive TUNEL staining, In addition to a possible role for this pr otein as a pro-apoptotic factor, SMN and its related protein share signific ant similarities in sequence and cellular function.