ALTERNATIVE SPLICING OF A NOVEL GLYCOPHORIN ALLELE GPHE(GL) GENERATES2 PROTEIN ISOFORMS IN THE HUMAN ERYTHROCYTE-MEMBRANE

The Henshaw antigen (synonym: He or MNS6) is carried by an altered for m of glycophorin B (GPB), but the molecular basis for its variable exp ression or quantitative polymorphism remains largely undefined. We rep ort here the identification and analysis of a novel glycophorin He all ele, GPHe(GL), which gives rise to the expression of two protein isofo rms in the erythrocyte membrane. In addition to the nucleotide changes defining the epitopic sequence of He, a single C-to-G nucleotide tran sversion in exon V coding for the membrane domain was found to cause a berrant RNA splicings by creating a new acceptor splice site. In addit ion, a T to-G transversion at -6 position of the acceptor splice site for exon IV was identified. Both full-length and truncated transcripts of GPHe(GL) were detected as the result of partial activation of the new acceptor splice site and partial inactivation of the normal splice sites. The full-length cDNA encoded He, S, and U antigens, whereas th e three truncated ones lacked either the sequence for S and U antigens or a large portion of the membrane domain or both. The GPB gene on th e other chromosome was apparently normal and its transcript encoded N, s, and U antigens. These results correlate alternative RNA splicing w ith the expression of two GPHe isoforms and thus delineate a new mecha nism for the phenotypic diversity of membrane glycophorins. (C) 1997 b y The American Society of Hematology.