Polypyrimidine tract binding protein blocks the 5′ splice site-dependent assembly of U2AF and the prespliceosomal e complex

Shalini Sharma, Arnold M. Falick, Douglas L. Black

Research output: Contribution to journalArticle

113 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)485-496
Number of pages12
JournalMolecular cell
Volume19
Issue number4
DOIs
StatePublished - Aug 19 2005
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this