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

By Gene W. Yeo, Nicole G. Coufal, Tiffany Y. Liang, Grace E. Peng, Xiang-Dong Fu, Fred H. Gage. Nature Structural &Molecular Biology, 2009

607 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0dda27ce79afcd406958b1792f7c2014589fe1b4

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Citations in the corpus

Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP (2010, methodology): “, 2008), FOX2 (Yeo et al., 2009) and SFRS1 (Sanford et al.”
TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. (2010, background): “Recent technologies coupled with high-throughput sequencing have yielded a global insight into RNA regulation (178,179), and such approaches are eagerly anticipated to understand the role of TDP-43 and FUS/TLS in neurodegeneration.”
Circular intronic long noncoding RNAs. (2013, methodology): “Native RNA-Protein Complex Immunoprecipitation, UV Crosslinking RIP, and Formaldehyde Crosslinking RIP Native RNA-protein complex immunoprecipitation (RIP) assays were carried out as previously described (Yin et al., 2012; Yeo et al., 2009; Niranjanakumari et al., 2002) with modifications.”
De novo mutations in Congenital Heart Disease with Neurodevelopmental and Other Birth Defects (2015, unknown): “Notably, we observed significant enrichment of damaging mutations in RBFOX2 target genes (17) in CHD cases (1.”
starBase: a database for exploring microRNA–mRNA interaction maps from Argonaute CLIP-Seq and Degradome-Seq data (2010, background): “In addition, we intend to integrate other CLIP-Seq data from other RNA binding proteins (51), such as PUM2 (22), Nova (52), FOX2 (53) and PTB (54), into starBase to improve our understanding of the eukaryotic regulatory networks.”