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Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB.
Nat Struct Mol Biol ; 17(9): 1114-23, 2010 Sep.
Article en En | MEDLINE | ID: mdl-20711188
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Empalme Alternativo / Proteína de Unión al Tracto de Polipirimidina Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Struct Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2010 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Empalme Alternativo / Proteína de Unión al Tracto de Polipirimidina Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Nat Struct Mol Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2010 Tipo del documento: Article Pais de publicación: Estados Unidos