The murine immunoglobulin alpha gene expresses multiple transcripts from a unique membrane exon.

Immunoglobulin heavy chains of each class exist in two forms, membrane (m) and secreted (s), which have different carboxy-terminal sequences encoded by different gene segments. We have sequenced the DNA spanning the coding region for the carboxy-terminal end of the alpha m chain in a BALB/c genomic clone and have examined alpha mRNA expression in transformed and normal B cells. Unlike the other murine heavy chain genes, which have two membrane exons (M1 and M2), the alpha gene has only one membrane exon (alpha M1). This unusual exon encodes a highly conserved transmembranal peptide plus flanking amino acids singular to IgA. The complexity of the alpha gene transcription is also unusual. Downstream of alpha M1, three AATAAA hexanucleotides are used to terminate as many as six distinct alpha membrane mRNAs. These appear to differ only in length and splicing pattern of their 3'-untranslated regions, and thus, encode the same alpha m protein. The alpha s protein is approximately 4000 daltons smaller than alpha m as judged by in vitro translation and is coded by a single 2.0-kb alpha s mRNA. We propose that the expression of alpha s and the multiple alpha m mRNAs is differentially controlled at the level of transcriptional termination.