UC Berkeley

By repressing translation and promoting mRNA decay, cells are able to modulate gene expression and respond swiftly to changing environmental signals and developmental cues. Although translation, storage and degradation of mRNAs are key steps in the post-transcriptional control of gene expression, how mRNAs transit between these processes remains poorly understood.

During my thesis I functionally characterized the DExD/H box ATPase Dhh1, a critical regulator of the cytoplasmic fate of mRNAs. Using mRNA tethering experiments in yeast, I showed that Dhh1 is sufficient to move an mRNA from an active state to translational repression. In actively dividing cells, translational repression is followed by mRNA decay, however, deleting components of the 5' to 3' decay pathway uncoupled these processes. Interestingly, Dhh1's ability to inactivate an mRNA coincided with its ability to move mRNAs into cytoplasmic processing bodies (P bodies).

I also examined the role of ATP hydrolysis in Dhh1's ability to repress translation and activate mRNA decay. While Dhh1's ATPase activity is not essential for translational inhibition and mRNA decay in dhh1Δ cells, I found that ATP hydrolysis regulates P body dynamics and the release of Dhh1 from these RNA-protein granules. Surprisingly, I found that the presence of a wild-type copy of Dhh1 rescues the abnormal P-body localization of a Dhh1 ATPase-mutant. Additionally, the Dhh1 ATPase mutant no longer reduces mRNA and protein levels when tethered to an mRNA in the presence of a wild-type copy of Dhh1. My results place Dhh1 at the interface of translation and decay controlling whether an mRNA is translated, stored or decayed.