Effect of upstream RNA processing on selection of mu S versus mu M poly(A)sites

All of the regulatory factors responsible for augmenting mu S mRNA levels p receding the dramatic increase in secretory IgM production upon B cell acti vation has not been totally elucidated. Whereas previous experiments have c entered on the region of the gene specifying the choice between splicing to mu M exons versus selection of the mu S poly(A) site, we have found that u pstream sequences within the C mu gene, specifically the C mu 4 acceptor sp lice site together with intronic sequences between the C mu 3 and C mu 4 ex ons, play an important role in dictating the precision or the extent of spl icing to the mu M exons even under conditions in which functional polyadeny lation factors should be in excess. Therefore, splicing of upstream exons c an affect remotely located downstream exons. These findings suggest that re gulation of differential mu S/mu M mRNA expression may involve general proc essing enzymes that recognize specific cis-regulatory sequences residing wi thin the body of the mu gene and account for the unique ability of activate d B cells to secrete copious amounts of IgM.