Puf3 contributes to changes in mRNA solubility, translation elongation dynamics at rare arginine codons and loss of protein homeostasis in cells lacking Not4

Ribosomes bound by Not5, in complex with Not4, are enriched for non-optimal codons in the A-site. Such ribosomes accumulate in cells lacking Not4 or Not5 that show defects in co-translational assembly and aggregation of new proteins.

Recently we observed that rapid depletion of Not1 and Not4 inversely regulates changes in mRNA solubility, correlating with codon-specific changes in A-site ribosome dwelling occupancies (RDOs). Here we describe that mRNAs less soluble upon Not4 depletion but more upon Not1 depletion are enriched for targets of the yeast Puf3 RNA binding protein. We determine that Puf3 is responsible for inverse changes of A-site RDOs upon Not1 and Not4 depletion, in particular at rare arginine codons, and it contributes to changes in mRNA solubility in the absence of Not4.