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Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome.
Nat Struct Mol Biol. 2008 Feb; 15(2):183-91.NS

Abstract

The polypyrimidine tract binding protein (PTB) binds pre-mRNAs to alter splice-site choice. We characterized a series of spliceosomal complexes that assemble on a pre-mRNA under conditions of either PTB-mediated splicing repression or its absence. In the absence of repression, exon definition complexes that were assembled downstream of the regulated exon could progress to pre-spliceosomal A complexes and functional spliceosomes. Under PTB-mediated repression, assembly was arrested at an A-like complex that was unable to transition to spliceosomal complexes. Trans-splicing experiments indicated that, even when the U1 and U2 small nuclear ribonucleoprotein particles (snRNPs) are properly bound to the upstream and downstream exons, the presence of PTB prevents the interaction of the two exon complexes. Proteomic analyses of these complexes provide a new description of exon definition complexes, and indicate that splicing regulators can act on the transition between the exon definition complex and an intron-defined spliceosome.

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 availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18193060

Citation

Sharma, Shalini, et al. "Polypyrimidine Tract Binding Protein Controls the Transition From Exon Definition to an Intron Defined Spliceosome." Nature Structural & Molecular Biology, vol. 15, no. 2, 2008, pp. 183-91.
Sharma S, Kohlstaedt LA, Damianov A, et al. Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome. Nat Struct Mol Biol. 2008;15(2):183-91.
Sharma, S., Kohlstaedt, L. A., Damianov, A., Rio, D. C., & Black, D. L. (2008). Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome. Nature Structural & Molecular Biology, 15(2), 183-91. https://doi.org/10.1038/nsmb.1375
Sharma S, et al. Polypyrimidine Tract Binding Protein Controls the Transition From Exon Definition to an Intron Defined Spliceosome. Nat Struct Mol Biol. 2008;15(2):183-91. PubMed PMID: 18193060.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome. AU - Sharma,Shalini, AU - Kohlstaedt,Lori A, AU - Damianov,Andrey, AU - Rio,Donald C, AU - Black,Douglas L, Y1 - 2008/01/13/ PY - 2007/10/18/received PY - 2007/12/13/accepted PY - 2008/1/15/pubmed PY - 2008/2/21/medline PY - 2008/1/15/entrez SP - 183 EP - 91 JF - Nature structural & molecular biology JO - Nat. Struct. Mol. Biol. VL - 15 IS - 2 N2 - The polypyrimidine tract binding protein (PTB) binds pre-mRNAs to alter splice-site choice. We characterized a series of spliceosomal complexes that assemble on a pre-mRNA under conditions of either PTB-mediated splicing repression or its absence. In the absence of repression, exon definition complexes that were assembled downstream of the regulated exon could progress to pre-spliceosomal A complexes and functional spliceosomes. Under PTB-mediated repression, assembly was arrested at an A-like complex that was unable to transition to spliceosomal complexes. Trans-splicing experiments indicated that, even when the U1 and U2 small nuclear ribonucleoprotein particles (snRNPs) are properly bound to the upstream and downstream exons, the presence of PTB prevents the interaction of the two exon complexes. Proteomic analyses of these complexes provide a new description of exon definition complexes, and indicate that splicing regulators can act on the transition between the exon definition complex and an intron-defined spliceosome. SN - 1545-9985 UR - https://www.unboundmedicine.com/medline/citation/18193060/Polypyrimidine_tract_binding_protein_controls_the_transition_from_exon_definition_to_an_intron_defined_spliceosome_ L2 - http://dx.doi.org/10.1038/nsmb.1375 DB - PRIME DP - Unbound Medicine ER -