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Nat Struct Mol Biol. 2010 Sep;17(9):1114-23. doi: 10.1038/nsmb.1881. Epub 2010 Aug 15.

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

Author information

1
Department of Biochemistry, University of Cambridge, Cambridge, UK.

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.

PMID:
20711188
PMCID:
PMC2933513
DOI:
10.1038/nsmb.1881
[Indexed for MEDLINE]
Free PMC Article

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