title: Alteration of splice site selection by an exon mutation in the human glycophorin A gene.
abstract: We report the identification in human glycophorin A gene of a novel exon mutation that affects splice site selection. DNA mapping showed that the mutation has abolished a unique MspI site marking the exon III-intron 3 splice junction (ACCG/GT). Genomic sequencing confirmed the occurrence of a single G-->A transition at the terminal nucleotide position of exon III. Analysis of the mRNA composition demonstrated a partial inactivation of the altered 5' splice site as well as skipping of exons involving the alternative use of other constitutive splice sites. The full-length transcript with the cognate A change encodes a variant glycophorin with an arginine replacing a glycine at position 59 and defining the ERIK epitope, whereas the exon III-deleted transcript specifies a shorter glycophorin carrying the Sta antigen. Also identified were the misspliced mRNA species with exon I-IV and exon I-V connections generated by selection of 5' splice sites far distant from the mutated site. Although having a correct translation frame, the predicted polypeptides of such exon-skipping products were not assembled on the erythrocyte membrane probably due to the severe truncation of the signal sequence required for targeting and translocation. These observations reveal a new mechanism for antigenic diversity of human glycophorins.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: C H
authors.initials: CH
authors.lastname: Huang
authors.forename: M
authors.initials: M
authors.lastname: Reid
authors.forename: G
authors.initials: G
authors.lastname: Daniels
authors.forename: O O
authors.initials: OO
authors.lastname: Blumenfeld
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D015342:DNA Probes; D005091:Exons; D006021:Glycophorins / Q000235:genetics*; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D015183:Restriction Mapping
chemical_list: D017931:DNA Primers; D015342:DNA Probes; D006021:Glycophorins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D004247:DNA