MULTIPLE FORMS OF MESSENGER-RNA ENCODING HUMAN PREGNANCY-ASSOCIATED ENDOMETRIAL ALPHA-2-GLOBULIN, A BETA-LACTOGLOBULIN HOMOLOG

Human pregnancy-associated endometrial alpha-2-globulin (alpha-2-PEG) is the major secretory protein product of the endometrium during embryo implantation and the first few weeks of pregnancy. It is a homologue of beta-lactoglobulin, a retinol binding protein, but unlike beta-lactoglobulin it is not found in the mammary gland. The cloning and sequencing of 34 alpha-2-PEG clones has revealed several minor variant forms indicative of alternatively spliced alpha-2-PEG pre-mRNA. These minor forms have also been detected amongst uncloned cDNA after PCR amplification. Some of these mRNAs would give rise to forms of alpha-2-PEG protein lacking internal sequences, whereas others affect the mRNA sequences on the 3' boundary of the presumed termination codon. Sequences within the cDNA clones are consistent with the existence of splice sites, and together with similarities found between alpha-2-PEG cDNA and beta-lactoglobulin gene sequences there is good evidence in support of an unusual scheme for the alternative splicing of alpha-2-PEG pre-mRNA involving both alternative 5' splice sites and alternative 3' splice sites. This scheme suggests that the alpha-2-PEG and beta-lactoglobulin genes share a similar structure in at least two regions, and it is likely that beta-lactoglobulin pre-mRNA would show a similar pattern of alternative splicing for one of these regions.