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

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

Author information

  • 1Crick-Jacobs Center for Theoretical and Computational Biology, Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. geneyeo@ucsd.edu

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.

PMID:
19136955
[PubMed - indexed for MEDLINE]
PMCID:
PMC2735254
Free PMC Article

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