Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping.
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.
Xue
Yuanchao
Y
Wuhan University, Hubei, China.
Zhou
Yu
Y
Wu
Tongbin
T
Zhu
Tuo
T
Ji
Xiong
X
Kwon
Young-Soo
YS
Zhang
Chao
C
Yeo
Gene
G
Black
Douglas L
DL
Sun
Hui
H
Fu
Xiang-Dong
XD
Zhang
Yi
Y
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
D038941:Polypyrimidine Tract-Binding Protein; D012313:RNA