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Polypyrimidine tract binding protein blocks the 5' splice site-dependent assembly of U2AF and the prespliceosomal E complex.
Mol Cell. 2005 Aug 19; 19(4):485-96.MC

Abstract

Polypyrimidine tract binding protein (PTB) represses some alternatively spliced exons by direct occlusion of splice sites. In repressing the splicing of the c-src N1 exon, we find that PTB acts by a different mechanism. PTB does not interfere with U1 snRNP binding to the N1 5' splice site. Instead, PTB prevents formation of the prespliceosomal early (E) complex across the intervening intron by preventing the assembly of the splicing factor U2AF on the 3' splice site of exon 4. When the unregulated 5' splice site of the upstream exon 3 is present, U2AF binding is restored and splicing between exons 3 and 4 proceeds in spite of the N1 exon bound PTB. Thus, rather than directly blocking the N1 splice sites, PTB prevents the 5' splice site-dependent assembly of U2AF into the E complex. This mechanism likely occurs in many other alternative exons.

Authors+Show Affiliations

Howard Hughes Medical Institute, University of California, Los Angeles, MRL5-748, Charles E. Young Drive South, Los Angeles, California 90095, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16109373

Citation

Sharma, Shalini, et al. "Polypyrimidine Tract Binding Protein Blocks the 5' Splice Site-dependent Assembly of U2AF and the Prespliceosomal E Complex." Molecular Cell, vol. 19, no. 4, 2005, pp. 485-96.
Sharma S, Falick AM, Black DL. Polypyrimidine tract binding protein blocks the 5' splice site-dependent assembly of U2AF and the prespliceosomal E complex. Mol Cell. 2005;19(4):485-96.
Sharma, S., Falick, A. M., & Black, D. L. (2005). Polypyrimidine tract binding protein blocks the 5' splice site-dependent assembly of U2AF and the prespliceosomal E complex. Molecular Cell, 19(4), 485-96.
Sharma S, Falick AM, Black DL. Polypyrimidine Tract Binding Protein Blocks the 5' Splice Site-dependent Assembly of U2AF and the Prespliceosomal E Complex. Mol Cell. 2005 Aug 19;19(4):485-96. PubMed PMID: 16109373.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polypyrimidine tract binding protein blocks the 5' splice site-dependent assembly of U2AF and the prespliceosomal E complex. AU - Sharma,Shalini, AU - Falick,Arnold M, AU - Black,Douglas L, PY - 2005/06/05/received PY - 2005/07/10/revised PY - 2005/07/25/accepted PY - 2005/8/20/pubmed PY - 2005/10/12/medline PY - 2005/8/20/entrez SP - 485 EP - 96 JF - Molecular cell JO - Mol. Cell VL - 19 IS - 4 N2 - Polypyrimidine tract binding protein (PTB) represses some alternatively spliced exons by direct occlusion of splice sites. In repressing the splicing of the c-src N1 exon, we find that PTB acts by a different mechanism. PTB does not interfere with U1 snRNP binding to the N1 5' splice site. Instead, PTB prevents formation of the prespliceosomal early (E) complex across the intervening intron by preventing the assembly of the splicing factor U2AF on the 3' splice site of exon 4. When the unregulated 5' splice site of the upstream exon 3 is present, U2AF binding is restored and splicing between exons 3 and 4 proceeds in spite of the N1 exon bound PTB. Thus, rather than directly blocking the N1 splice sites, PTB prevents the 5' splice site-dependent assembly of U2AF into the E complex. This mechanism likely occurs in many other alternative exons. SN - 1097-2765 UR - https://www.unboundmedicine.com/medline/citation/16109373/Polypyrimidine_tract_binding_protein_blocks_the_5'_splice_site_dependent_assembly_of_U2AF_and_the_prespliceosomal_E_complex_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1097-2765(05)01478-4 DB - PRIME DP - Unbound Medicine ER -