An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells.

Journal: 
Nat Struct Mol Biol
Publication Year: 
2009
Authors: 
Gene W Yeo , Nicole G Coufal , Tiffany Y Liang , Grace E Peng , Xiang-Dong Fu , Fred H Gage
Public Summary: 
Scientific Abstract: 
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.

© 2013 California Institute for Regenerative Medicine