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
in En
| MEDLINE
| ID: mdl-20711188
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alternative Splicing
/
Polypyrimidine Tract-Binding Protein
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nat Struct Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
Year:
2010
Document type:
Article
Affiliation country:
United kingdom