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

Nat Struct Mol Biol. 2009 Feb;16(2):130-7. doi: 10.1038/nsmb.1545. Epub 2009 Jan 11.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Cell Survival
  • Embryonic Stem Cells / metabolism*
  • Exons
  • Humans
  • Immunoprecipitation
  • RNA Splice Sites*
  • RNA Splicing Factors
  • RNA-Binding Proteins / metabolism*
  • Repressor Proteins / metabolism*
  • Sequence Analysis, RNA


  • RBFOX2 protein, human
  • RNA Splice Sites
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • Repressor Proteins