An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells.
The elucidation of a code for regulated splicing has been a long-standing goal in understanding the control of post-transcriptional gene expression events that are crucial for cell survival, differentiation and development. We decoded functional RNA elements in vivo by constructing an RNA map for the cell type-specific splicing regulator FOX2 (also known as RBM9) via cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) in human embryonic stem cells. The map identified a large cohort of specific FOX2 targets, many of which are themselves splicing regulators, and comparison between the FOX2 binding profile and validated splicing events revealed a general rule for FOX2-regulated exon inclusion or skipping in a position-dependent manner. These findings suggest that FOX2 functions as a critical regulator of a splicing network, and we further show that FOX2 is important for the survival of human embryonic stem cells.
Yeo
Gene W
GW
Crick-Jacobs Center for Theoretical and Computational Biology, Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. geneyeo@ucsd.edu
Coufal
Nicole G
NG
Liang
Tiffany Y
TY
Peng
Grace E
GE
Fu
Xiang-Dong
XD
Gage
Fred H
FH
D017398:Alternative Splicing; D002470:Cell Survival; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005091:Exons; D006801:Humans; D047468:Immunoprecipitation; D022821:RNA Splice Sites; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D017423:Sequence Analysis, RNA
C454924:RBFOX2 protein, human; D022821:RNA Splice Sites; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D012097:Repressor Proteins