Selective stalling of human translation through small molecule engagement of the ribosome nascent chain

We use ribosome profiling to demonstrate the selectivity of a small molecule, PF-06446846 that inhibits translation of its target by selectively inducing ribosome-stalling in a nascent chain sequence dependent manner. Overall design: Study 1: Huh7 cells were treated with 1.5 µM PF-06446846, 0.3 µM PF-06446846 or vehicle for 10 or 60 minutes, and subjected to ribosome profiling. This study included three biological replicates Study 2: Huh7 cells were treated with 1.5 µM PF-06446846 or vehicle for 60 minutes and subjected to both ribosome profiling and mRNA-seq. This study included two biological replicates.