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Fig. 4 | BMC Cancer

Fig. 4

From: Oncogenic KRAS alters splicing factor phosphorylation and alternative splicing in lung cancer

Fig. 4

A screen for splicing alterations in lung cancer identifies alternative splicing events regulated by KRAS. A Number of events differentially spliced between cells with variant alleles and cells with respective wild-type alleles. KRASG12C and KRASG12V are starred and labeled. Colors represent the five splicing event categories considered. FDR < 0.05. ∆PSI > 10%. B Change in exon levels in cassette exons differentially expressed in both KRASG12V compared to KRASWT and KRASG12C compared to KRASWT (Pearson’s coefficient = 0.71, p-value = 0.020). ∆PSI = Change in Percent Spliced In. C Schematic of MAZ-1 and MAZ-2 isoforms with labeled active stop codons. Shown are the pre-mRNA structures and the spliced mRNA with untranslated regions grayed out. Arrows above the spliced mRNAs indicate qRT-PCR primer binding sites. D Percent read coverage of MAZ exon V′ in KRASWT, KRASG12V, and KRASG12C overexpressing A549 cells (left) and KRASWT, KRASG12V, and KRASQ61H overexpressing AALE cells (right), relative to the expression of flanking exons. Inset zooms in on cassette exon. E Quantitative levels of MAZ-2 relative to MAZ-1 isoforms in AALE cells overexpressing KRAS or RIT1 variants, normalized to KRASWT or RIT1WT, as measured by qRT-PCR. Error bars = standard error

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