Fig. 4: Modeling SRSF1 phosphorylation in MM drives interactome dynamics but not global splicing changes. | Nature Communications

Fig. 4: Modeling SRSF1 phosphorylation in MM drives interactome dynamics but not global splicing changes.

From: Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma

Fig. 4

a Cartoon of protein architecture for SRSF1-NLS-mCherry-[FLAG]3. b Epi-fluorescent images of DAPI-stained AMO-1-expressing mCherry-labeled SRSF1-WT (top panels), SRSF1-SD (middle panels), and SRSF1-SA (bottom panels). Scale bar represents 10 μm, DAPI stain is pseudo-colored in blue and mCherry is pseudo-colored in red in the merged image, and micrographs represent experiments repeated twice with similar results. c, d Histograms of ΔPSI for IR, alt. exon donor, alt. exon acceptor, alt. first exon, and alt. last exon ASEs when comparing differential splicing of AMO-1-expressing c SRSF1-WT treated with 15 nM Cfz to DMSO and d SD to WT. e Volcano plots indicating differential interactors of SD compared to WT in both the nucleus and cytoplasm. f Volcano plots of WT or SD when compared to control (NLS-mCherry-[FLAG]3) in AMO-1 nucleus reveal SD exclusion from spliceosome. Significant enriched proteins in pink, unenriched proteins in cyan (p < 0.05, ≥2-fold change). Circle size corresponds to summed LFQ intensities. mCherry ratio is red and SRSF1 ratio is yellow.

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