Alternative processing of IgA pre-mRNA responds like IgM to alterations in the efficiency of the competing splice and cleavage-polyadenylation reactions.
Both the membrane-associated and -secreted Ig proteins are encoded by a single gene whose primary transcript is alternatively processed at its 3' end. The relative use of the alternative processing pathways is regulated during B cell maturation. This alternative RNA processing involves two competing reactions, splicing from the last constant region exon to the membrane exon(s) and cleavage-polyadenylation at the secretory-specific poly(A) site. Studies with the IgM-encoding mu gene have shown that cell-specific regulation requires that the efficiencies of these two reactions be balanced; any gene modifications that substantially improve or reduce the efficiency of either reaction also abrogate the regulatory shift in alternative processing pathways. All of the Ig isotypes that undergo a membrane-to-secreted switch during B cell maturation have a similar gene structure, thus suggesting that they might all be regulated by the same mechanism. We show that RNA processing of chimeric mu alpha genes containing modifications in the C alpha 3 exon size and the C alpha 3-alpha m intron size respond to these modifications as predicted by previous mu gene studies. In addition, RNA expression ratios from the chimeric mu alpha genes are regulated in B cells and plasma cells. This provides good evidence that splicing and cleavage-polyadenylation in the alpha gene are balanced reactions that are regulated in the same way as in the mu gene.
Seipelt
R L
RL
Department of Microbiology and Immunology, University of Kentucky College of Medicine, Lexington 40536, USA.
Peterson
M L
ML
D017398:Alternative Splicing; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D005091:Exons / Q000235:genetics; D007137:Immunoglobulin alpha-Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D066298:In Vitro Techniques; D007438:Introns / Q000235:genetics; D051379:Mice; D009694:Nucleic Acid Precursors / Q000378:metabolism*; D010950:Plasma Cells / Q000378:metabolism; D011061:Poly A / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics
D007137:Immunoglobulin alpha-Chains; D007148:Immunoglobulin mu-Chains; D009694:Nucleic Acid Precursors; D012322:RNA Precursors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D011061:Poly A