title: Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping.
abstract: 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.
authors.affiliation: Wuhan University, Hubei, China.
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Xue
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Tongbin
authors.initials: T
authors.lastname: Wu
authors.forename: Tuo
authors.initials: T
authors.lastname: Zhu
authors.forename: Xiong
authors.initials: X
authors.lastname: Ji
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Kwon
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Gene
authors.initials: G
authors.lastname: Yeo
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Black
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D005091:Exons / Q000235:genetics*; D020869:Gene Expression Profiling; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000235:genetics / Q000378:metabolism
chemical_list: D038941:Polypyrimidine Tract-Binding Protein; D012313:RNA