GENOMIC ORGANIZATION OF THE HUMAN NSP GENE, PROTOTYPE OF A NOVEL GENEFAMILY ENCODING RETICULONS

Recently, cDNA cloning and expression of three mRNA variants of the hu man NSP gene were described. This neuroendocrine-specific gene encodes three NSP protein isoforms with unique amino-terminal parts, but comm on carboxy-terminal parts. The proteins, with yet unknown function, ar e associated with the endoplasmic reticulum and therefore are named NS P reticulons. Potentially, these proteins are neuroendocrine markers o f a novel category in human lung cancer diagnosis. Here, the genomic o rganization of this gene was studied by analysis of genomic clones iso lated from lambda phage and YAC libraries. The NSP exons were found to be dispersed over a genomic region of about 275 kb. The present eluci dation of the genomic organization of the NSP gene explains the genera tion of NSP mRNA variants encoding NSP protein isoforms. Multiple prom oters rather than alternative splicing of internal exons seem to be in volved in this diversity. Furthermore, comparison of NSP genomic and c DNA sequences with databank nucleotide sequences resulted in the disco very of other human members of this novel family of reticulons encodin g genes. (C) 1996 Academic Press. Inc.