The DEAD-box protein Dhh1 promotes decapping by slowing ribosome movement.

Abstract

Translational control and messenger RNA (mRNA) decay represent important control points in the regulation of gene expression. In yeast, the major pathway for mRNA decay is initiated by deadenylation followed by decapping and 5'-3' exonucleolytic digestion of the mRNA. Proteins that activate decapping, such as the DEAD-box RNA helicase Dhh1, have been postulated to function by limiting translation initiation, thereby promoting a ribosome-free mRNA that is targeted for decapping. In contrast to this model, we show here that Dhh1 represses translation in vivo at a step subsequent to initiation. First, we establish that Dhh1 represses translation independent of initiation factors eIF4E and eIF3b. Second, we show association of Dhh1 on an mRNA leads to the accumulation of ribosomes on the transcript. Third, we demonstrate that endogenous Dhh1 accompanies slowly translocating polyribosomes. Lastly, Dhh1 activates decapping in response to impaired ribosome elongation. Together, these findings suggest that changes in ribosome transit rate represent a key event in the decapping and turnover of mRNA.