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The polypyrimidine tract binding protein binds upstream of neural cell-specific c-src exon N1 to repress the splicing of the intron downstream.
Mol Cell Biol. 1997 Aug; 17(8):4667-76.MC

Abstract

The neural cell-specific N1 exon of the c-src pre-mRNA is both negatively regulated in nonneural cells and positively regulated in neurons. We previously identified conserved intronic elements flanking N1 that direct the repression of N1 splicing in a nonneural HeLa cell extract. The upstream repressor elements are located within the polypyrimidine tract of the N1 exon 3' splice site. A short RNA containing this 3' splice site sequence can sequester trans-acting factors in the HeLa extract to allow splicing of N1. We now show that these upstream repressor elements specifically interact with the polypyrimidine tract binding protein (PTB). Mutations in the polypyrimidine tract reduce both PTB binding and the ability of the competitor RNA to derepress splicing. Moreover, purified PTB protein restores the repression of N1 splicing in an extract derepressed by a competitor RNA. In this system, the PTB protein is acting across the N1 exon to regulate the splicing of N1 to the downstream exon 4. This mechanism is in contrast to other cases of splicing regulation by PTB, in which the protein represses the splice site to which it binds.

Authors+Show Affiliations

Molecular Biology Institute, University of California, Los Angeles, USA.No 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

9234723

Citation

Chan, R C., and D L. Black. "The Polypyrimidine Tract Binding Protein Binds Upstream of Neural Cell-specific C-src Exon N1 to Repress the Splicing of the Intron Downstream." Molecular and Cellular Biology, vol. 17, no. 8, 1997, pp. 4667-76.
Chan RC, Black DL. The polypyrimidine tract binding protein binds upstream of neural cell-specific c-src exon N1 to repress the splicing of the intron downstream. Mol Cell Biol. 1997;17(8):4667-76.
Chan, R. C., & Black, D. L. (1997). The polypyrimidine tract binding protein binds upstream of neural cell-specific c-src exon N1 to repress the splicing of the intron downstream. Molecular and Cellular Biology, 17(8), 4667-76.
Chan RC, Black DL. The Polypyrimidine Tract Binding Protein Binds Upstream of Neural Cell-specific C-src Exon N1 to Repress the Splicing of the Intron Downstream. Mol Cell Biol. 1997;17(8):4667-76. PubMed PMID: 9234723.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The polypyrimidine tract binding protein binds upstream of neural cell-specific c-src exon N1 to repress the splicing of the intron downstream. AU - Chan,R C, AU - Black,D L, PY - 1997/8/1/pubmed PY - 1997/8/1/medline PY - 1997/8/1/entrez SP - 4667 EP - 76 JF - Molecular and cellular biology JO - Mol. Cell. Biol. VL - 17 IS - 8 N2 - The neural cell-specific N1 exon of the c-src pre-mRNA is both negatively regulated in nonneural cells and positively regulated in neurons. We previously identified conserved intronic elements flanking N1 that direct the repression of N1 splicing in a nonneural HeLa cell extract. The upstream repressor elements are located within the polypyrimidine tract of the N1 exon 3' splice site. A short RNA containing this 3' splice site sequence can sequester trans-acting factors in the HeLa extract to allow splicing of N1. We now show that these upstream repressor elements specifically interact with the polypyrimidine tract binding protein (PTB). Mutations in the polypyrimidine tract reduce both PTB binding and the ability of the competitor RNA to derepress splicing. Moreover, purified PTB protein restores the repression of N1 splicing in an extract derepressed by a competitor RNA. In this system, the PTB protein is acting across the N1 exon to regulate the splicing of N1 to the downstream exon 4. This mechanism is in contrast to other cases of splicing regulation by PTB, in which the protein represses the splice site to which it binds. SN - 0270-7306 UR - https://www.unboundmedicine.com/medline/citation/9234723/The_polypyrimidine_tract_binding_protein_binds_upstream_of_neural_cell_specific_c_src_exon_N1_to_repress_the_splicing_of_the_intron_downstream_ L2 - http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=9234723 DB - PRIME DP - Unbound Medicine ER -