Genomic organization and isoform-specific tissue expression of human NAPOR(CUGBP2) as a candidate gene for familial arrhythmogenic right ventriculardysplasia

Neuroblastoma apoptosis-related RNA-binding protein (NAPOR; HGMW-approved s ymbol CUGBP2) is a newly discovered gene prominently induced during apoptos is, suggesting that: it plays a role during apoptosis, We have found that i t is encoded by a gene located on chromosome 10p13-p14 between Genethon mar kers D10S547 and D10S223, a region to which we have recently localized a ge ne responsible for arrhythmogenic right ventricular dysplasia (ARVD). To ex amine its possible role in the pathogenesis of ARVD, we determined the geno mic organization of the human NAPOR gene including its exon-intron boundari es and the putative promoter sequence, which provide a plausible mechanism for its alternative mRNA splicing. We also demonstrated that three isoforms of the NAPOR transcript were differently expressed, with NAPOR-3 being nea rly neuron specific while the other two forms were ubiquitously expressed. The expression of NAPOR is differentially regulated during development. Fin ally, we screened the members of the ARVD family for mutations and identifi ed two DNA sequence variants in the protein-coding exons of NAPOR, neither of which was responsible for ARVD, While the function of NAPOR remains to b e elucidated, our current characterization of the NAPOR gene will be valuab le for further clinical and functional study, (C) 2001 Academic Press.