Regulated immunoglobulin (Ig) RNA processing does not require specific cis-acting sequences: Non-Ig RNA can be alternatively processed in B cells and plasma cells

Alternative RNA processing of the heavy-chain immunoglobulin μ gene is regulated during B-cell maturation and requires competition between splice and cleavage-polyadenylation reactions that have balanced efficiencies. Studies with modified μ genes have failed to identify gene-specific sequences required for regulation. Thus, the only important feature for regulation may be the balanced competing splice and cleavage-polyadenylation reactions themselves. If this is so, then alternative RNA processing from any gene with similar competitive RNA processing pathways should also be regulated when expression is compared between B cells and plasma cells. To test this prediction, two nonimmunoglobulin genes engineered to have competing splice and cleavage-polyadenylation reactions were expressed in B cells and plasma cells. The ratios of alternative RNAs produced from both genes are different in the two cell types; like the μ gene, relatively more spliced RNA is produced in B cells than in plasma cells. Also, in a survey of μ gene expression in nine non-B-cell lines, only a T-cell line had an expression pattern similar to that of B cells; the expression patterns of all other lines resembled that of the plasma cells. Therefore, regulated μ RNA processing must be mediated by changes in general processing factors whose activity or abundance is regulated, most likely, in B cells.