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The Journal of Immunology, 2000, 164: 3659-3665.
Copyright © 2000 by The American Association of Immunologists

Correct Immunoglobulin {alpha} mRNA Processing Depends on Specific Sequence in the C{alpha}3-{alpha}M Intron1

John H. Coyle and Deborah A. Lebman2

Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298.

The maturation of IgM-expressing B cells to IgM-secreting plasma cells is associated with both an increase in µ mRNA and the ratio of secreted to membrane forms of µ mRNA which differ at the 3' termini. In contrast, both in vitro and in vivo the secreted form of {alpha} mRNA is predominant at all stages in the development of a secretory IgA response. Previous studies demonstrated that preferential usage of the {alpha}s poly(A) site does not result from transcription termination and is independent of either the poly(A) sites or the 3' splice site associated with the exon encoding the membrane exon of IgA ({alpha}M). The present study demonstrates that a 349-bp region located 774 bp 3' to the {alpha}s poly(A) site is required for the preferential usage of the {alpha}s terminus. This region, which is the first isotype-specific cis-acting regulatory sequence not immediately adjacent to a secretory poly(A) site to be identified, contains regulatory elements that increase the efficiency of polyadenylation/cleavage. A ubiquitous, ~58-kDa RNA-binding protein interacts specifically with this regulatory region. These studies support the premise that cis-acting elements unique to each CH gene can impinge upon a common mechanism regulating Ig mRNA processing.




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