Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome

Shalini Sharma, Lori A. Kohlstaedt, Andrey Damianov, Donald C. Rio, Douglas L. Black

Research output: Contribution to journalArticle

107 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)183-191
Number of pages9
JournalNature Structural and Molecular Biology
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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