A novel translational control mechanism involving RNA structures within coding sequences

The impact of RNA structures in coding sequences (CDS) within mRNAs is poorly understood. Here 31 we identify a novel and highly conserved mechanism of translational control involving RNA 32 structures within coding sequences and the DEAD-box helicase Dhh1. Using yeast genetics and 33 genome-wide ribosome profiling analyses we show that this mechanism, initially derived from studies 34 of the Brome Mosaic virus RNA genome, extends to yeast and human mRNAs highly enriched in 35 membrane and secreted proteins. All Dhh1-dependent mRNAs, viral and cellular, share key common 36 features. First, they contain long and highly structured CDSs, including a region located around 37 nucleotide 70 after the translation initiation site, second, they are directly bound by Dhh1 with a 38 specific binding distribution and third, complementary experimental approaches suggest that they are 39 activated by Dhh1 at the translation initiation step. Our results show that ribosome translocation is not 40 the only unwinding force of CDS and uncover a novel layer of translational control that involves RNA 41 helicases and RNA folding within CDS providing novel opportunities for regulation of membrane and 42 secretome proteins.