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Polypyrimidine tract-binding protein positively regulates inclusion of an alternative 3'-terminal exon.
Mol Cell Biol. 1999 Jan; 19(1):78-85.MC

Abstract

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.

Authors+Show Affiliations

Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA. hlou@bcm.tmc.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9858533

Citation

Lou, H, et al. "Polypyrimidine Tract-binding Protein Positively Regulates Inclusion of an Alternative 3'-terminal Exon." Molecular and Cellular Biology, vol. 19, no. 1, 1999, pp. 78-85.
Lou H, Helfman DM, Gagel RF, et al. Polypyrimidine tract-binding protein positively regulates inclusion of an alternative 3'-terminal exon. Mol Cell Biol. 1999;19(1):78-85.
Lou, H., Helfman, D. M., Gagel, R. F., & Berget, S. M. (1999). Polypyrimidine tract-binding protein positively regulates inclusion of an alternative 3'-terminal exon. Molecular and Cellular Biology, 19(1), 78-85.
Lou H, et al. Polypyrimidine Tract-binding Protein Positively Regulates Inclusion of an Alternative 3'-terminal Exon. Mol Cell Biol. 1999;19(1):78-85. PubMed PMID: 9858533.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polypyrimidine tract-binding protein positively regulates inclusion of an alternative 3'-terminal exon. AU - Lou,H, AU - Helfman,D M, AU - Gagel,R F, AU - Berget,S M, PY - 1998/12/22/pubmed PY - 1998/12/22/medline PY - 1998/12/22/entrez SP - 78 EP - 85 JF - Molecular and cellular biology JO - Mol Cell Biol VL - 19 IS - 1 N2 - 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. SN - 0270-7306 UR - https://www.unboundmedicine.com/medline/citation/9858533/Polypyrimidine_tract_binding_protein_positively_regulates_inclusion_of_an_alternative_3'_terminal_exon_ L2 - https://journals.asm.org/doi/10.1128/MCB.19.1.78?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -