Multiple transcripts of the murine immunoglobulin epsilon membrane locus are generated by alternative splicing and differential usage of two polyadenylation sites.

The human C epsilon gene produces a number of alternatively spliced heavy chain transcripts of which some encode functional IgE isoforms. We now show that differentially processed epsilon mRNA variants also exist in the mouse and are generated by differential polyadenylation and alternative splicing of primary epsilon chain transcripts. The two poly(A) sites of the mouse membrane transcripts were identified in the present study by RACE-PCR analysis. The first poly(A) site is located 743 nt downstream from the beginning of the second membrane exon (M2) and contains the same non-consensus AGTAAA signal sequence as the single poly(A) site of the human membrane transcripts. The second poly(A) site is located almost 500nt further downstream and is characterized by an AAGAAA hexamer. This poly(A) site contains a (G+T) rich element downstream to the site of cleavage and polyadenylation and is preferentially utilized by the membrane epsilon transcripts. Additional diversity of epsilon transcripts is generated by alternative splicing between the last constant region exon (CH4) and the two membrane exons (M1 and M2). The alternatively spliced transcripts include two variants that skip the first membrane exon and encode epsilon heavy chains that lack the transmembrane domain. The third variant is generated by splicing to an internal site in M2 and codes for a membrane isoform that is 10 amino acids shorter in the cytoplasmic domain than the classical membrane IgE. Although little amino-acid sequence homology exists between the murine epsilon chain isoforms and their human counterparts, the pattern of splicing is rather conserved between the two species.