Exon size affects competition between splicing and cleavage-polyadenylation in the immunoglobulin μ gene

The alternative RNA processing of μs and μm mRNAs from a single primary transcript depends on competition between a cleavage-polyadenylation reaction to produce μs mRNA and a splicing reaction to produce μm mRNA. The ratio of μs to μm mRNA is regulated during B-cell maturation; relatively more spliced μm mRNA is made in B cells than in plasma cells. The balance between the efficiencies of splicing and cleavage-polyadenylation is critical to the regulation. The μ gene can be modified to either reduce or improve the efficiency of each reaction and thus alter the ratio of the two RNAs produced. However, as long as neither reaction is so strong that it totally dominates, expression of the modified μ, genes is regulated in B cells and plasma cells. The current experiments reveal a relationship between the Cμ4 exon size and the μs/μm expression ratio. The shorter the distance between the Cμ,4 5′ splice site and the nearest upstream 3′ splice site, the more spliced μm mRNA was produced. Conversely, when this exon was expanded, more μs mRNA was produced. Expression from these μ. genes with altered exon sizes were regulated between B cells and plasma cells. Since RNA processing in the μ gene can be considered a competition between defining the Cμ4 exon as an internal exon (in μs mRNA) versus a terminal exon (in μs mRNA), exon size may affect the competition among factors interacting with this exon.