Fig. 2: Depletion of mHtt enhances protein synthesis and increases the speed of ribosome translocation.

A Representative immunoblots performed on CRISPR/Cas9 Htt-depleted mouse striatal cells after puromycin metabolic labeling. B, C quantifications of the blots from A showing levels of Htt (B), puromycin incorporation (C) in control (Ctrl) and Htt-depleted control, HD-homo striatal cells. Data are mean ± SEM (n = 9 independent experiments), ***P < 0.001 and ****P < 0.0001 one-way ANOVA followed by Bonferroni’s multiple comparisons test. D–F Representative polysome profiles (D) obtained from wtHtt-depleted mouse striatal cells before (basal, E) and after ribosome run-off assay using harringtonine (2 µg/ml, 2 min, F) and their corresponding quantification of polysome to monosome (PS/MS) ratios (area under the curve). Data are mean ± SEM (n = 3 independent experiments), *P < 0.05 by two-tailed Student’s t test, n.s not significant. G–I Representative polysome profiles (G) obtained from mHtt-depleted mouse striatal cells before (basal, H) and after ribosome run-off assay using harringtonine (2 min, I) and their corresponding quantification of polysome to monosome (PS/MS) ratios (area under the curve). Data are mean ± SEM (H, n = 3; I, n = 4 independent experiments), **P < 0.01 by two-tailed Student’s t test, n.s not significant. J, K Representative polysome profiles (J) obtained from wtHtt- and mHtt-depleted mouse striatal cells after ribosome run-off assay using harringtonine (2 min), and their corresponding quantification of polysome to monosome (PS/MS) ratios (K). Data are mean ± SEM (wtHtt depleted, n = 5; mHtt depleted, n = 6 independent experiments), **P < 0.01 by two-tailed Student’s t test. n.s not significant. Exact P values are reported in the Source Data file. Source data are provided as a Source Data file.