Fig. 5.

Rumpelstiltskin, homolog of human hnRNPM, is a strong modifier of MATR3 toxicity. a Schematic of candidate RNAi screen in MATR3 Drosophila model. Diagrammatic representation of MATR3 protein interactors that were screened for suppression of MATR3-mediated toxicity. hnRNPM homolog in Drosophila, Rumpelstiltskin (rump), is a unique suppressor of MATR3 toxicity. b Quantification of egg-to-adult viability in flies expressing MATR3 with and without rump RNAi. Constitutive ubiquitous expression of S85C with rump knockdown rescues S85C-mediated developmental toxicity (n = 3, One-way ANOVA). c Kaplan–Meier survival curve of adults ubiquitously expressing MATR3 S85C, d MATR3 F115C and e MATR3 WT, with and without rump knockdown. Knocking down rump significantly improved longevity of F115C and S85C-expressing flies and had no obvious effect on WT longevity (n = 50, Log-rank Mantel-Cox test). f Median survival of MATR3-expressing flies with and without rump KD showed increased median survival upon rump KD in F115C- and S85C-expressing flies g Immunoblot of NP40-soluble and NP40-insoluble fractions of MATR3 in Drosophila thorax expressing MATR3, with or without rump RNAi, in the muscles. α-tubulin is used as loading control. h Quantification of the insoluble/soluble MATR3 protein fractions. Rump KD decreased insolubility of MATR3 S85C (n = 6 per group; One-way ANOVA). Error bars indicate S.E.M. ***p < 0.001; ****p < 0.0001