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mRNA stability is substantially dictated by the action of the ribosome

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There are several mRNA surveillance pathways in eukaryotes (NGD, NSD and NMD ) that moderate the effects of natural errors in the cell and more broadly regulate gene expression. We have previously defined biochemical parameters of the factors Dom34, Hbs1 and Rli1 and their role on the ribosome in NGD and NSD using our previously developed in vitro reconstituted yeast translation system. We have correlated these biochemical observations with ribosome profiling experiments to broadly define the in vivo targets of these same mRNA surveillance pathways. We are currently combining these same approaches to better define the mechanism of action of the translational repressor Dhh1. These studies argue that Dhh1 senses ribosome speed and communicates that information to the mRNA decay machinery such that mRNA half lives are correlated with codon optimality.

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