Fig. 3: R-MCD expression drives dose-dependent sequestration of GA-rich genes in nuclear speckles.
From: Collective homeostasis of condensation-prone proteins via their mRNAs
a, AlphaFold prediction of the PPIGLCD structure and the representation of amino acids within the domain. b, Expression of PPIGLCD over time after doxycycline (dox) induction from a single experiment. c, Nuclear–cytoplasmic distribution of mRNAs with different degrees of GA multivalency in response to different timepoints of PPIGLCD expression. n = 6,367, 566 and 141 genes for the bottom 90%, top 10% and top 2%, respectively, with calculations performed on values from 4 independent replicates. d, The change in proportion of labelled peptides after 8 h of SILAC labelling per protein when inducing PPIGLCD expression for 12 h compared with uninduced cells. The boxplots show the mean change per protein across replicates, and the dot plots show the mean across all proteins for a given replicate (n = 4 independent experiments). e,f, Example images from a set of three independent experiments showing the HCR-FISH signal for PSAP (control; e) or BRD4 (GA multivalent; f) mRNAs, with SC35 immunofluorescence and mScarlet–PPIGLCD. g, Quantification of the enrichment of the HCR-FISH signal within nuclear speckles versus the nucleoplasm per nucleus with respect to PPIGLCD expression. Three independent replicates are plotted in different colours, and regression slopes are plotted in dashed lines. h, The slopes of linear regression models of the relationship between mScarlet–PPIGLCD expression and mRNA enrichment within the speckle for control and GA-multivalent mRNAs. Pairwise significance testing were performed using FDR-corrected Welch t-tests, where *P < 0.05, **P < 0.01 and ***P < 0.001. Precise P values can be found in the Source Data. The boxplots show the median (centre), upper and lower quartiles (hinges), and the nearest value within 1.5 times the interquartile range from the quartile (whiskers). Black dashed lines denote no change between conditions or no correlation, as appropriate.
