[PDF][PDF] Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping
Molecular cell, 2009•cell.com
Recent transcriptome analysis indicates that> 90% of human genes undergo alternative
splicing, underscoring the contribution of differential RNA processing to diverse proteomes
in higher eukaryotic cells. The polypyrimidine tract-binding protein PTB is a well-
characterized splicing repressor, but PTB knockdown causes both exon inclusion and
skipping. Genome-wide mapping of PTB-RNA interactions and construction of a functional
RNA map now reveal that dominant PTB binding near a competing constitutive splice site …
splicing, underscoring the contribution of differential RNA processing to diverse proteomes
in higher eukaryotic cells. The polypyrimidine tract-binding protein PTB is a well-
characterized splicing repressor, but PTB knockdown causes both exon inclusion and
skipping. Genome-wide mapping of PTB-RNA interactions and construction of a functional
RNA map now reveal that dominant PTB binding near a competing constitutive splice site …
Summary
Recent transcriptome analysis indicates that > 90% of human genes undergo alternative splicing, underscoring the contribution of differential RNA processing to diverse proteomes in higher eukaryotic cells. The polypyrimidine tract-binding protein PTB is a well-characterized splicing repressor, but PTB knockdown causes both exon inclusion and skipping. Genome-wide mapping of PTB-RNA interactions and construction of a functional RNA map now reveal that dominant PTB binding near a competing constitutive splice site generally induces exon inclusion, whereas prevalent binding close to an alternative site often causes exon skipping. This positional effect was further demonstrated by disrupting or creating a PTB-binding site on minigene constructs and testing their responses to PTB knockdown or overexpression. These findings suggest a mechanism for PTB to modulate splice site competition to produce opposite functional consequences, which may be generally applicable to RNA-binding splicing factors to positively or negatively regulate alternative splicing in mammalian cells.
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