title: A single point mutation results in A allele-specific exon skipping in the bovine alpha s1-casein mRNA.
abstract: Bovine alpha s1-casein (alpha s1-CN) allele A is found in low allelic frequencies among different cattle breeds and is known to be characterized by the deletion of amino-acid residues 14 to 26 of the mature protein (as defined via the most common allele B), and a corresponding deletion of 39 bp from its cDNA. Based upon the genomic sequence of bovine alpha s1-CN [Koczan et al., Nucleic Acids Res. 19 (1991) 5591-5596], this allelic deviation can be interpreted as an absence of exon 4 from the A allele mRNA and protein product. We demonstrate that this allelic aberration is not caused by a genomic deletion across the exon-4 DNA, but is correlated with a single point mutation at position +6 in the splice donor sequence distal of exon 4, which results in upstream exon skipping during the serial splice reactions of the A allele alpha s1-CN pre-mRNA. The A-allele-specific mutation at position +6 is able to interrupt the perfect complementarity of the intron-4 splice donor signal (positions one to eight) with U1-snRNA, which may then no longer be able to compensate for a rather weak exon-4 upstream splice acceptor sequence in facilitating the initial binding of U2 auxiliary factor/65-kDa (U2AF65) to that polypyrimidine tract. This interpretation of the exon skipping mechanism in alpha s1-CN allele A is in agreement with similar results obtained [Hoffmann and Grabowski, Genes Dev. 6 (1992) 2554-2568] in an analysis of the rat preprotachykinin-encoding gene and in vitro experiments.
authors.affiliation: Institut für Tierzucht und Haustiergenetik, Justus-Liebig-Universität Giessen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Mohr
authors.forename: D
authors.initials: D
authors.lastname: Koczan
authors.forename: D
authors.initials: D
authors.lastname: Linder
authors.forename: G
authors.initials: G
authors.lastname: Hobom
authors.forename: G
authors.initials: G
authors.lastname: Erhardt
mesh_terms: D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002364:Caseins / Q000235:genetics*; D002417:Cattle; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D002364:Caseins; D012333:RNA, Messenger