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The secretory-specific poly(A) signal (mus) of the immunoglobulin mu gene plays a central role in regulating alternative RNA processing to produce RNAs that encode membrane-associated and secreted immunoglobulins. This poly(A) signal is in direct competition with a splice reaction, and regulation requires that these two reaction efficiencies be balanced. The mus poly(A) signal has several unique sequence features that may contribute to its strength and regulation. Site-directed mutations and small internal deletions made in the intact mu gene show that an extensive AU/A-rich sequence surrounding AAUAAA enhances signal use and that, of the two potential downstream GU-rich elements, both of which appear suboptimally located, only the proximal GU-rich sequence contributes substantially to use of this signal. A GU-rich sequence placed at a more standard location did not improve mus poly(A) signal use. All mu genes tested that contained modified mus poly(A) signals were developmentally regulated, indicating that the GU-rich sequences, the sequences between them previously identified as suboptimal U1A binding sites, and an upstream suboptimal U1A site do not contribute to mu mRNA processing regulation. Expression of wild-type and modified mu genes in HeLa cells overexpressing U1A also failed to demonstrate that U1A contributes to mus poly(A) signal regulation.

Multiple Features Contribute to the Use of the Immunoglobulin M Secretion-Specific Poly(A) Signal but Are Not Required for Developmental Regulation