Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB

Llorian, Miriam; Schwartz, Schraga; Clark, Tyson A; Hollander, Dror; Tan, Lit-Yeen; Spellman, Rachel; Gordon, Adele; Schweitzer, Anthony C; de la Grange, Pierre; Ast, Gil; Smith, Christopher W J
September 2010
Nature Structural & Molecular Biology;Sep2010, Vol. 17 Issue 9, p1114
Academic Journal
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.


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