title: Non-AUG start codons responsible for ABO weak blood group alleles on initiation mutant backgrounds.
abstract: Histo-blood group ABO gene polymorphism is crucial in transfusion medicine. We studied the activity and subcellular distribution of ABO gene-encoded A glycosyltransferases with N-terminal truncation. We hypothesized that truncated enzymes starting at internal methionines drove the synthesis of oligosaccharide A antigen in those already described alleles that lack a proper translation initiation codon. Not only we tested the functionality of the mutant transferases by expressing them and assessing their capacity to drive the appearance of A antigen on the cell surface, but we also analyzed their subcellullar localization, which has not been described before. The results highlight the importance of the transmembrane domain because proteins deprived of it are not able to localize properly and deliver substantial amounts of antigen on the cell surface. Truncated proteins with their first amino acid well within the luminal domain are not properly localized and lose their enzymatic activity. Most importantly, we demonstrated that other codons than AUG might be used to start the protein synthesis rather than internal methionines in translation-initiation mutants, explaining the molecular mechanism by which transferases lacking a classical start codon are able to synthesize A/B antigens.
authors.affiliation: Laboratory of Immunohematology and Glycobiology, Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, Badalona, Barcelona, Spain.
authors.forename: Emili
authors.initials: E
authors.lastname: Cid
authors.affiliation: Laboratory of Immunohematology and Glycobiology, Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, Badalona, Barcelona, Spain.
authors.forename: Miyako
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Immunohematology and Glycobiology, Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, Badalona, Barcelona, Spain.|Program of Predictive and Personalized Medicine of Cancer (PMPPC), Institut d'Investigació Germans Trias i Pujol (IGTP), Campus Can Ruti, Badalona, Barcelona, Spain.
authors.forename: Fumiichiro
authors.initials: F
authors.lastname: Yamamoto
mesh_terms: D000017:ABO Blood-Group System / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D018387:Codon, Initiator; D005434:Flow Cytometry; D005647:Fucosyltransferases / Q000235:genetics / Q000276:immunology; D000068617:Genetic Background; D006801:Humans; D009154:Mutation; D014176:Protein Biosynthesis; D021381:Protein Transport; D017384:Sequence Deletion; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D000017:ABO Blood-Group System; D018387:Codon, Initiator; D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase