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

Miriam Llorian, Schraga Schwartz, Tyson A. Clark, Dror Hollander, Lit Yeen Tan, Rachel Spellman, Adele Gordon, Anthony C. Schweitzer, Pierre De La Grange, Gil Ast, Christopher W.J. Smith

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1114-1123
Number of pages10
JournalNature Structural and Molecular Biology
Volume17
Issue number9
DOIs
StatePublished - Sep 2010

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