ABO blood group A transferases catalyze the biosynthesis of FORS blood group FORS1 antigen upon deletion of exon 3 or 4

Blood Advances
Miyako YamamotoF Yamamoto

Abstract

Evolutionarily related ABO and GBGT1 genes encode, respectively, A and B glycosyltransferases (AT and BT) and Forssman glycolipid synthase (FS), which catalyze the biosynthesis of A and B, and Forssman (FORS1) oligosaccharide antigens responsible for the ABO and FORS blood group systems. Humans are a Forssman antigen-negative species; however, rare individuals with Apae phenotype express FORS1 on their red blood cells. We previously demonstrated that the replacement of the LeuGlyGly tripeptide sequence at codons 266 to 268 of human AT with GBGT1-encoded FS-specific GlyGlyAla enabled the enzyme to produce FORS1 antigen, although the FS activity was weak. We searched for additional molecular mechanisms that might allow human AT to express FORS1. A variety of derivative expression constructs of human AT were prepared. DNA was transfected into COS1 (B3GALNT1) cells, and cell-surface expression of FORS1 was immunologically monitored. To our surprise, the deletion of exon 3 or 4, but not of exon 2 or 5, of human AT transcripts bestowed moderate FS activity, indicating that the A allele is inherently capable of producing a protein with FS activity. Because RNA splicing is frequently altered in cancer, this mechanism may explain, at le...Continue Reading

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Citations

Jul 23, 2019·European Journal of Cardiovascular Nursing : Journal of the Working Group on Cardiovascular Nursing of the European Society of Cardiology·Daria SegevAyelet Dunsky
Nov 3, 2021·Chembiochem : a European Journal of Chemical Biology·Emili CidFumiichiro Yamamoto

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