Tags

Type your tag names separated by a space and hit enter

Repression of alpha-actinin SM exon splicing by assisted binding of PTB to the polypyrimidine tract.
RNA. 2007 Aug; 13(8):1214-23.RNA

Abstract

Polypyrimidine tract binding protein (PTB) acts as a regulatory repressor of a large number of alternatively spliced exons, often requiring multiple binding sites in order to repress splicing. In one case, cooperative binding of PTB has been shown to accompany repression. The SM exon of the alpha-actinin pre-mRNA is also repressed by PTB, leading to inclusion of the alternative upstream NM exon. The SM exon has a distant branch point located 386 nt upstream of the exon with an adjacent 26 nucleotide pyrimidine tract. Here we have analyzed PTB binding to the NM and SM exon region of the alpha-actinin pre-mRNA. We find that three regions of the intron bind PTB, including the 3' end of the polypyrimidine tract (PPT) and two additional regions between the PPT and the SM exon. The downstream PTB binding sites are essential for full repression and promote binding of PTB to the PPT with a consequent reduction in U2AF(65) binding. Our results are consistent with a repressive mechanism in which cooperative binding of PTB to the PPT competes with binding of U2AF(65), thereby specifically blocking splicing of the SM exon.

Authors+Show Affiliations

Department of Biochemistry, University of Cambridge, UK.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17592047

Citation

Matlin, Arianne J., et al. "Repression of Alpha-actinin SM Exon Splicing By Assisted Binding of PTB to the Polypyrimidine Tract." RNA (New York, N.Y.), vol. 13, no. 8, 2007, pp. 1214-23.
Matlin AJ, Southby J, Gooding C, et al. Repression of alpha-actinin SM exon splicing by assisted binding of PTB to the polypyrimidine tract. RNA. 2007;13(8):1214-23.
Matlin, A. J., Southby, J., Gooding, C., & Smith, C. W. (2007). Repression of alpha-actinin SM exon splicing by assisted binding of PTB to the polypyrimidine tract. RNA (New York, N.Y.), 13(8), 1214-23.
Matlin AJ, et al. Repression of Alpha-actinin SM Exon Splicing By Assisted Binding of PTB to the Polypyrimidine Tract. RNA. 2007;13(8):1214-23. PubMed PMID: 17592047.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Repression of alpha-actinin SM exon splicing by assisted binding of PTB to the polypyrimidine tract. AU - Matlin,Arianne J, AU - Southby,Justine, AU - Gooding,Clare, AU - Smith,Christopher W J, Y1 - 2007/06/25/ PY - 2007/6/27/pubmed PY - 2007/8/31/medline PY - 2007/6/27/entrez SP - 1214 EP - 23 JF - RNA (New York, N.Y.) JO - RNA VL - 13 IS - 8 N2 - Polypyrimidine tract binding protein (PTB) acts as a regulatory repressor of a large number of alternatively spliced exons, often requiring multiple binding sites in order to repress splicing. In one case, cooperative binding of PTB has been shown to accompany repression. The SM exon of the alpha-actinin pre-mRNA is also repressed by PTB, leading to inclusion of the alternative upstream NM exon. The SM exon has a distant branch point located 386 nt upstream of the exon with an adjacent 26 nucleotide pyrimidine tract. Here we have analyzed PTB binding to the NM and SM exon region of the alpha-actinin pre-mRNA. We find that three regions of the intron bind PTB, including the 3' end of the polypyrimidine tract (PPT) and two additional regions between the PPT and the SM exon. The downstream PTB binding sites are essential for full repression and promote binding of PTB to the PPT with a consequent reduction in U2AF(65) binding. Our results are consistent with a repressive mechanism in which cooperative binding of PTB to the PPT competes with binding of U2AF(65), thereby specifically blocking splicing of the SM exon. SN - 1355-8382 UR - https://www.unboundmedicine.com/medline/citation/17592047/Repression_of_alpha_actinin_SM_exon_splicing_by_assisted_binding_of_PTB_to_the_polypyrimidine_tract_ L2 - http://www.rnajournal.org/cgi/pmidlookup?view=long&pmid=17592047 DB - PRIME DP - Unbound Medicine ER -