Regulated production of μ(m) and μ(s) mRNA requires linkage of the poly(A) addition sites and is dependent on the length of the μ(s)-μ(m) intron

mRNAs encoding the membrane-associated (μ(m)) and secreted (μ(s)) forms of μ heavy chain are derived from transcripts of the same immunoglobulin gene by differential RNA processing. To help elucidate the mechanism that regulates the production of these two μ mRNAs during the course of B-lymphoid maturation, we produced a series of specifically modified μ-chain genes and studied their expression when transfected into cells representing either early or late developmental stages. We have established that proper regulation depends on linkage of the μ(s) and μ(m) poly(A) addition sites and the length of the μ(s)-μ(m) intron. Deletion of an 800- to 900-nucleotide segment from the central region of this intron abolishes regulation; replacement of this segment with miscellaneous DNA sequences restores it. From these results we propose a model in which regulation is principally achieved by competition between cleavage/polyadenylylation of the μ(s) site and splicing of the C(μ)4 and μ(m) exons.