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1.  HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism 
Cell reports  2014;6(6):1139-1152.
Summary
The RNA-binding proteins Rbfox1/2/3 regulate alternative splicing in the nervous system, and disruption of Rbfox1 has been implicated in autism. However, comprehensive identification of functional Rbfox targets has been challenging. Here we performed HITS-CLIP for all three Rbfox family members to globally map, at a single-nucleotide resolution, their in vivo RNA interaction sites in the mouse brain. We found that the two guanines in the Rbfox-binding motif UGCAUG are critical for protein-RNA interactions and crosslinking. Using integrative modeling, these interaction sites combined with additional datasets defined 1,059 direct Rbfox target alternative splicing events. Over half of the quantifiable targets show dynamic changes during brain development. Of particular interest are 111 events from 48 candidate autism-susceptibility genes, including syndromic autism genes Shank3, Cacna1c, and Tsc2. Alteration of Rbfox targets in some autistic brains is correlated with down-regulation of all three Rbfox proteins, supporting the potential clinical relevance of the splicing- regulatory network.
doi:10.1016/j.celrep.2014.02.005
PMCID: PMC3992522  PMID: 24613350
2.  ONCOGENIC SPLICING FACTOR SRSF1 IS A CRITICAL TRANSCRIPTIONAL TARGET OF MYC 
Cell reports  2012;1(2):110-117.
The SR protein splicing factor SRSF1 is a potent proto-oncogene that is frequently upregulated in cancer. Here we show that SRSF1 is a direct target of the transcription-factor oncoprotein MYC. These two oncogenes are significantly co-expressed in lung carcinomas, and MYC knockdown downregulates SRSF1 expression in lung-cancer cell lines. MYC directly activates transcription of SRSF1 through two non-canonical E-boxes in its promoter. The resulting increase in SRSF1 protein is sufficient to modulate alternative splicing of a subset of transcripts. In particular, MYC induction leads to SRSF1-mediated alternative splicing of the signaling kinase MKNK2 and the transcription factor TEAD1. SRSF1 knockdown reduces MYC’s oncogenic activity, decreasing proliferation and anchorage-independent growth. These results suggest a mechanism for SRSF1 upregulation in tumors with elevated MYC, and identify SRSF1 as a critical MYC target that contributes to its oncogenic potential by enabling MYC to regulate the expression of specific protein isoforms through alternative splicing.
doi:10.1016/j.celrep.2011.12.001
PMCID: PMC3334311  PMID: 22545246

Results 1-2 (2)