Fig. 1: Poly-PR and Poly-GR inhibit mammalian translation, comparable to some small-molecule translation inhibitors.
From: Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM

a Comparison of translation inhibition by PR20 and GR20 to that by harringtonine, cycloheximide, and GDPCP upon a 5-min preincubation with rabbit reticulocyte lysates prior to addition of nanoluciferase mRNA (t = 0). IC50 of PR20 and GR20 are similar to those of cycloheximide, harringtonine, and GDPCP (n = 3 independent experiments, mean ± SEM; RLU, relative luminescence units). b Comparison of translation inhibition by PR20 and GR20 to that by harringtonine, cycloheximide, and GDPCP. The inhibitors were added 300–400 s (gaps in the curves) after addition of nanoluciferase mRNA. PR20 and GR20 act similarly to elongation inhibitors cycloheximide and GDPCP (n = 3 independent experiments, mean ± SEM). c Comparison of polysome profiles of rabbit reticulocyte lysate translating endogenous mRNA in the presence of translation inhibitors (Abs254, UV absorbance at 254 nm). The translation mixture was incubated for 5 min at 30 °C in the presence or absence of PR20, GR20, harringtonine, cycloheximide, and GDPCP (n = 2 independent experiments, representative traces with concurrent uninhibited control are shown). Half-mer peaks (black arrows) are most prominent with PR20, GR20, and GDPCP. Source data are provided as a Source Data file.