Effect of upstream RNA processing on selection of μS versus μM poly(A) sites

Abstract

All of the regulatory factors responsible for augmenting μS mRNA levels preceding the dramatic increase in secretory IgM production upon B cell activation has not been totally elucidated. Whereas previous experiments have centered on the region of the gene specifying the choice between splicing to μM exons versus selection of the μS poly(A) site, we have found that upstream sequences within the Cμ gene, specifically the Cμ4 acceptor splice site together with intronic sequences between the Cμ3 and Cμ4 exons, play an important role in dictating the precision or the extent of splicing to the μM exons even under conditions in which functional polyadenylation factors should be in excess. Therefore, splicing of upstream exons can affect remotely located downstream exons. These findings suggest that regulation of differential μS/μM mRNA expression may involve general processing enzymes that recognize specific cis-regulatory sequences residing within the body of the μ gene and account for the unique ability of activated B cells to secrete copious amounts of IgM.