SRA

By using ribosome profiling, we demonstrate that catalytic activity of the RNA helicase DDX3 is generally required for mediating translation repression under stress. Intriguingly, however, a cancer-related DDX3 variant DDX3 R534H selectively preserves translation of genes encoding core nucleosome components. Additionally, DDX3 variants also shift ORF usage on select genes, such as RPLP1 and stress-response factors as an added mechanism of translation regulation during stress. Thus, DDX3 through both extensive and selective interactions with RNA and the ribosomal machinery helps to remodel the translational landscape under stress and in cancer. Overall design: Cells expressing either DDX3 WT or R534H variant were treated with or without sodium arsenite and lysed in the presence of cyclohexime. Ribosome-protected mRNA fragments after RNase I treatment were recovered and sequenced.