Poly(A) site choice rather than splice site choice governs the regulated production of IgM heavy-chain RNAs.

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Abstract
Alternative processing of the immunoglobulin .mu. primary transcript results in regulated production of mRNAs encoding the secreted (.mu.s) and membrane-bound (.mu.m) form of IgM heavy chain during B-cell development. To elucidate the basis for this control, we analyzed the expression of altered forms of the .mu. transcription unit. Deletion of intron sequence between the .mu.s and .mu.m exons, which reduces the distance between the two poly(A) sites as well as the distance between .mu.m splice sites, enhances production of .mu.m RNA. Correct expression is restored by insertion of heterologous sequences, demonstrating that spacing is indeed the critical aspect. The altered spacing appears to affect poly(A) site usage rather than splice site usage, since it was the distance between the poly (A) sites rather than the distance between splice sites that was found to be decisive. Finally, removal of either the C.mu.4 splice donor or the m1 splice acceptor, thus eliminating normal .mu.m splicing, does not increase usage of the .mu.s poly(A) site. We therefore conclude that the major factor in determining the ratio of .mu.s to .mu.m is a poly(A) site choice rather than a splicing choice.