Fig. 6: NF1 exon23a splicing in HGG is controlled by differential expression of the CELF/ELAVL gene families.
From: Splicing is an alternate oncogenic pathway activation mechanism in glioma
a Scatter plot comparing log2 fold change in expression between pHGG and normal brain of splice factors and RNA-binding proteins, with the enrichment of the RNA motifs they bind in introns surrounding differentially spliced exons in pHGG. b Motifs and enrichment in up- and downstream introns surrounding differentially spliced exons for the indicated splicing factors. c Expression ratio (log2 fold change) of negative (blue) and positive (red) NF1 exon23a splicing regulators between pHGG (n = 64) and normal brain (n = 20). Box shows IQR with the median marked, and the whiskers show the range. P values: CELF2, 0.0001; CELF3, 4 × 10−16; CELF4, 7 × 10−28; CELF5, 2 × 10−26; CELF6, 0.001; ELAVL2, 0.0003; ELAVL3, 0.0001; ELAVL4, 1.5 × 10−5; MBNL2, 0.01, MBNL3, 7 × 10−5. d U343 GBM cells transduced with control (EV) lentivirus or expressing CELF4 or ELAVL3 were analyzed by RT-PCR for the indicated splicing events. Bands corresponding to NF1-II (includes exon23a, red box) and NF1-I are shown at the left. Gels are representative of two experiments. e Bubble plot showing the relationship between NF1 exon23a splicing regulators and NF1 exon23a inclusion and RAS activity score (ES, enrichment score from ssGSEA) in pHGG. Bubble color represents Pearson correlation, size is significant, and statistically significant correlations have a black border on the bubble. Statistical tests: t (c, e). *P < 0.05, **P < 0.01, ***P < 0.001. Source data are provided as a Source Data file.
