EXON SIZE AFFECTS COMPETITION BETWEEN SPLICING AND CLEAVAGE-POLYADENYLATION IN THE IMMUNOGLOBULIN-MU GENE

The alternative RNA processing of mus and mum mRNAs from a single primary transcript depends on competition between a cleavage-polyadenylation reaction to produce mus mRNA and a splicing reaction to produce mum mRNA. The ratio of mus to mum mRNA is regulated during B-cell maturation; relatively more spliced mum 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 mu 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 mu genes is regulated in B cells and plasma cells. The current experiments reveal a relationship between the Cmu4 exon size and the mus/mum expression ratio. The shorter the distance between the Cmu4 5' splice site and the nearest upstream 3' splice site, the more spliced mum mRNA was produced. Conversely, when this exon was expanded, more mus mRNA was produced. Expression from these mu genes with altered exon sizes were regulated between B cells and plasma cells. Since RNA processing in the mu gene can be considered a competition between defining the Cmu4 exon as an internal exon (in mum mRNA) versus a terminal exon (in mus mRNA), exon size may affect the competition among factors interacting with this exon.