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Molecular and Cellular Biology, July 2004, p. 6162-6171, Vol. 24, No. 14
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.14.6162-6171.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

U1A Inhibits Cleavage at the Immunoglobulin M Heavy-Chain Secretory Poly(A) Site by Binding between the Two Downstream GU-Rich Regions

Catherine Phillips,* Niseema Pachikara, and Samuel I. Gunderson

Nelson Labs, Rutgers University, Piscataway, New Jersey 08854

Received 3 March 2004/ Returned for modification 29 March 2004/ Accepted 21 April 2004

The immunoglobulin M heavy-chain locus contains two poly(A) sites which are alternatively expressed during B-cell differentiation. Despite its promoter proximal location, the secretory poly(A) site is not expressed in undifferentiated cells. Crucial to the activation of the secretory poly(A) site during B-cell differentiation are changes in the binding of cleavage stimulatory factor 64K to GU-rich elements downstream of the poly(A) site. What regulates this change is not understood. The secretory poly(A) site contains two downstream GU-rich regions separated by a 29-nucleotide sequence. Both GU-rich regions are necessary for binding of the specific cleavage-polyadenylation complex. We demonstrate here that U1A binds two (AUGCN1-3C) motifs within the 29-nucleotide sequence and inhibits the binding of cleavage stimulatory factor 64K and cleavage at the secretory poly(A) site.

* Corresponding author. Mailing address: Molecular Biology and Biochemistry, Rutgers University, Nelson Labs, Room A322, 604 Allison Rd., Piscataway, NJ 08854. Phone: (732) 445-1017. Fax: (732) 445-4213. E-mail: Cphillips{at}biology.rutgers.edu.

Molecular and Cellular Biology, July 2004, p. 6162-6171, Vol. 24, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.14.6162-6171.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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