Fig. 1

An in vivo RNAi screen identified Ref1 among RNA-binding protein genes as a modifier of TDP-43 and ATXN2-32Q toxicity. a Screen overview. b Heatmap of modifiers identified in the screen. Enhancers in shades of red and suppressors in green. c Ref1 knockdown does not affect the mRNA level of a reporter LacZ transgene. n.s. not statistically significant, two-tailed Student’s t-test. d Ref1 knockdown does not affect the β-galactosidase protein levels produced from a reporter LacZ transgene. n.s. not statistically significant, two-tailed Student’s t-test. Genotypes for (c) and (d). Control RNAi: GMR-GAL4, UAS-LacZ/+; UAS-control RNAi (JF01355)/+. Ref1 RNAi: GMR-GAL4, UAS-LacZ/+; UAS-Ref1 RNAi (HMS01301)/+. e External image (top) and cross section (bottom) of the fly eye. Genotype: YH3-GAL4/UAS-control RNAi (JF01355). f Ref1 RNAi suppresses TDP-43-mediated neurodegeneration. Genotypes. Control: UAS-TDP-43/+; YH3-GAL4/UAS-control RNAi (JF01355). Ref1: UAS-TDP-43/+; YH3-GAL4/UAS-Ref1 RNAi (HMS01301). Quantification of retinal area from Drosophila head sections shown on the right. ***p < 0.001, two-tailed Student’s t-test. g Ref1 RNAi suppresses TDP-43+ ATXN2(32Q)-mediated neurodegeneration. Genotypes. Control: UAS-TDP-43, UAS-ATXN2-32Q/+; YH3-GAL4/UAS-control RNAi (JF01355). Ref1: UAS-TDP-43, UAS-ATXN2-32Q /+; YH3-GAL4/UAS-Ref1 RNAi (HMS01301). Quantification of retinal area shown on the right. ***p < 0.001 two-tailed Student’s t-test. For all graphs, individual data points are shown with mean +/− standard deviation