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Molecular and Cellular Biology, January 1999, p. 78-85, Vol. 19, No. 1
Verna and Marrs McLean Department of
Biochemistry,
Received 29 July 1998/Returned for modification 10 September
1998/Accepted 14 October 1998
Polypyrimidine tract-binding protein (PTB) is an abundant
vertebrate hnRNP protein. PTB binding sites have been found within introns both upstream and downstream of alternative exons in a number
of genes that are negatively controlled by the binding of PTB. We have
previously reported that PTB binds to a pyrimidine tract within an RNA
processing enhancer located adjacent to an alternative 3'-terminal exon
within the gene coding for calcitonin and calcitonin gene-related
peptide. The enhancer consists of a pyrimidine tract and CAG directly
abutting on a 5' splice site sequence to form a pseudoexon. Here we
show that the binding of PTB to the enhancer pyrimidine tract is
functional in that exon inclusion increases when in vivo levels of PTB
increase. This is the first example of positive regulation of exon
inclusion by PTB. The binding of PTB was antagonistic to the binding of U2AF to the enhancer-located pyrimidine tract. Altering the enhancer pyrimidine tract to a consensus sequence for the binding of U2AF eliminated enhancement of exon inclusion in vivo and exon
polyadenylation in vitro. An additional PTB binding site was identified
close to the AAUAAA hexanucleotide sequence of the exon 4 poly(A) site. These observations suggest a dual role for PTB in
facilitating recognition of exon 4: binding to the enhancer pyrimidine
tract to interrupt productive recognition of the enhancer pseudoexon by
splicing factors and interacting with the poly(A) site to positively affect polyadenylation.
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Polypyrimidine Tract-Binding Protein Positively
Regulates Inclusion of an Alternative 3'-Terminal Exon
*
Corresponding author. Mailing address: Verna and Marrs
McLean Department of Biochemistry, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-4622. Fax: (713) 795-5487. E-mail: hlou{at}bcm.tmc.edu.
Molecular and Cellular Biology, January 1999, p. 78-85, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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