COMPLEX ALTERNATIVE RNA SPLICING OF EPSILON-IMMUNOGLOBULIN TRANSCRIPTS PRODUCES MESSENGER-RNAS ENCODING 4 POTENTIAL SECRETED PROTEIN ISOFORMS

In RNA from human IgE-producing lymphocytes, we previously discovered two alternatively spliced epsilon-immunoglobulin mRNA isoforms that en code a novel secreted form of IgE and a membrane-bound species. Furthe r analysis using epsilon-specific reverse transcriptase polymerase cha in reactions has elucidated several additional alternatively spliced s pecies of epsilon mRNA. One RNA isoform is generated by splicing the C H4 exon to a novel distal splice acceptor site, forming an epsilon RNA species (designated CH4-M2'') that encodes a secreted epsilon protein 6 amino acids larger than the classic secreted epsilon protein. The o ther three novel epsilon RNAs are generated by splicing from within CH 4 to a new exon structure (designated CH5) that is located between CH4 and the membrane exons. Since the three new mRNAs using CH5 share the same stop codon in CH5, they all encode the same novel protein, which is 10 amino acids shorter than the classic secreted epsilon heavy cha in. The new alternatively spliced epsilon mRNAs reported here, in addi tion to the previously reported forms encoding membrane and larger sec reted IgE, appear to reflect the normal splicing pattern in humans, as we have detected all these epsilon RNAs in all the human IgE-secretin g cells and cell lines tested.