PREDOMINANT USAGE OF THE PROXIMAL POLY(A) SITE IN ALPHA MESSENGER-RNAS IS NOT INTRINSIC TO THE 3' TERMINI

The maturation of IGM-expressing a cells to IgM-secreting plasma cells is associated with both an increase in mu mRNA and the ratio of secre ted to membrane forms of mu mRNA, In contrast, previous studies demons trated that in vitro the secreted form of alpha mRNA (alpha s mRNA) pr edominates regardless of the stage of a cell differentiation, The pres ent study demonstrates that as mRNA predominates in both a cells deriv ed from the germinal centers of murine Peyer's patches and in the func tional IgA memory population, suggesting that in vitro events accurate ly represent the generation of a secretory IgA response in vivo. Altho ugh the predominant usage of the as poly(A) site is due to RNA process ing, it does not depend on either the as poly(A) site, the 3' splice s ite associated with the exon encoding the membrane exon of IgA (alpha M) or the alpha M poly(A) sites. Analysis of the sequence of the intro n between the as terminus and alpha M (alpha s-alpha M intron) demonst rates the existence of several potential regulatory elements, Furtherm ore, the effects of deletions within the alpha s-alpha M intron on 3' terminus usage demonstrate that the predominant usage of the proximal terminus is not strictly dependent on the length of the intron, Togeth er with previous work, these observations support the idea that choice of 3' terminus for ail Ig heavy chain genes is regulated by a similar mechanism, but specific sequences within a heavy chain gene can impin ge upon that mechanism.