Fig. 4: ZNF598 regulates the quality control of stalled translation of C9ALS-associated poly(GR) and rescues poly(GR)-induced toxicity in Drosophila and patient cell models. | Nature Communications

Fig. 4: ZNF598 regulates the quality control of stalled translation of C9ALS-associated poly(GR) and rescues poly(GR)-induced toxicity in Drosophila and patient cell models.

From: Stalled translation by mitochondrial stress upregulates a CNOT4-ZNF598 ribosomal quality control pathway important for tissue homeostasis

Fig. 4

a Immunoblots showing the effect of ZNF598-HA OE on the level of Flag-tagged GR80 expressed in fly muscle. b Effect of ZNF598-HA OE on wing posture in Mhc>GR80 flies. c Immunoblots showing effect of ZNF598 RNAi on the level of FLAG-tagged GR80 in Mhc>GR80 flies. d Effect of ZNF598-RNAi on wing posture in Mhc>GR80 flies. e Effect of ZNF598 OE on mitochondrial morphology in Mhc > GR80 fly muscle, which normally exhibits vacuolated and disconnected mitochondria. f Dot blots showing effect of ZNF598 OE or RNAi on poly(GR) protein level in C9ALS patient fibroblasts. g Immunoblots showing effect of ASCC3 or ZNF598 silencing, or ZNF598 OE, on Flag-GR80 protein expression in HELA cells. Effect of ZNF598 on mitochondrial calcium stained by Rhod-2AM (h) and MMP stained by TMRM (i) in C9ALS fibroblasts. GFP was co-transfected with ZNF598 at 1:3 ratio so that virtually all ZNF598 transfected cells would be marked with GFP. Bar graphs show data quantification. j Effect of ZNF598 siRNA on MMP stained by TMRM in C9ALS fibroblasts. Bar graph shows data quantification. Data are representative of at least three biologically independent experiments (mean ± SD), n = 3. Representative blot or image is from at least three independent experiments with similar results. p-values were calculated by unpaired two-tailed t-test. Source data are provided as a Source Data file.

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