title: Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB.
abstract: To gain global insights into the role of the well-known repressive splicing regulator PTB, we analyzed the consequences of PTB knockdown in HeLa cells using high-density oligonucleotide splice-sensitive microarrays. The major class of identified PTB-regulated splicing event was PTB-repressed cassette exons, but there was also a substantial number of PTB-activated splicing events. PTB-repressed and PTB-activated exons showed a distinct arrangement of motifs with pyrimidine-rich motif enrichment within and upstream of repressed exons but downstream of activated exons. The N-terminal half of PTB was sufficient to activate splicing when recruited downstream of a PTB-activated exon. Moreover, insertion of an upstream pyrimidine tract was sufficient to convert a PTB-activated exon to a PTB-repressed exon. Our results show that PTB, an archetypal splicing repressor, has variable splicing activity that predictably depends upon its binding location with respect to target exons.
authors: Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors: Miriam
authors: M
authors: Llorian
authors: Schraga
authors: S
authors: Schwartz
authors: Tyson A
authors: TA
authors: Clark
authors: Dror
authors: D
authors: Hollander
authors: Lit-Yeen
authors: LY
authors: Tan
authors: Rachel
authors: R
authors: Spellman
authors: Adele
authors: A
authors: Gordon
authors: Anthony C
authors: AC
authors: Schweitzer
authors: Pierre
authors: P
authors: de la Grange
authors: Gil
authors: G
authors: Ast
authors: Christopher W J
authors: CW
authors: Smith
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D005091:Exons; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D037941:Silencer Elements, Transcriptional
chemical_list: D038941:Polypyrimidine Tract-Binding Protein