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Molecular and Cellular Biology, September 2006, p. 6762-6771, Vol. 26, No. 18
0270-7306/06/$08.00+0     doi:10.1128/MCB.00889-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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

Martha L. Peterson,^* Gina L. Bingham, and Clarissa Cowan

Department of Microbiology, Immunology and Molecular Genetics, Department of Pathology and Laboratory Medicine, and Lucille Parker Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40536

Received 18 May 2006/ Returned for modification 27 June 2006/ Accepted 29 June 2006

The secretory-specific poly(A) signal (µs) of the immunoglobulin µ 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 µs 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 µ 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 µs poly(A) signal use. All µ genes tested that contained modified µs 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 µ mRNA processing regulation. Expression of wild-type and modified µ genes in HeLa cells overexpressing U1A also failed to demonstrate that U1A contributes to µs poly(A) signal regulation.

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* Corresponding author. Mailing address: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, 800 Rose St., 108A Combs Building, Lexington, KY 40536-0096. Phone: (859) 257-5478. Fax: (859) 323-2094. E-mail: mlpete01{at}uky.edu.

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Molecular and Cellular Biology, September 2006, p. 6762-6771, Vol. 26, No. 18
0270-7306/06/$08.00+0     doi:10.1128/MCB.00889-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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