Cloning and characterization of the gene encoding human NPL4, a protein interacting with the ubiquitin fusion-degradation protein (UFD1L)

The ubiquitin fusion-degradation gene (UFDIL) encodes the human homologue o f the yeast ubiquitin fusion-degradation 1 protein, an essential component of the ubiquitin-dependent proteolytic turnover and mRNA processing. Althou gh the UFDIL gene has been mapped in the region commonly deleted in patient s with DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS), correlatio n between its haploinsufficiency and the phenotype has not yet been establi shed. The only functional data available about mammalian Ufd1p is the abili ty to form a complex with the rat Npl4 protein, a component of the nuclear pore complex. In this paper we report the cloning and molecular characteriz ation of the human NPL4 gene. This gene encodes for a protein 96% homologou s to the rat Npl4, and 44 and 34% homologous to the C. elegans and S. cerev isiae Npl4 gene products, respectively. Fluorescence in situ hybridization experiments on human metaphases localized the NPL4 gene on the most telomer ic region of chromosome 17q. Northern blots analysis on foetal and adult hu man tissues revealed a major similar to4.5 kb transcript most abundant in h eart, brain, kidney and skeletal muscle. In order to test a potential relat ionship between nuclear transport defects and some aspect of the DGS/VCFS p henotype, we also exclude the presence of mutations in the NPL4 coding sequ ence in a subset of patients with DGS/VCFS and no detectable 22q11 deletion or mutations at the UFDIL locus. (C) 2001 Elsevier Science B.V. All fights reserved.