Genome Biology, 2023, 24, 30
We demonstrated that mRNA solubility defines the dynamics of co-translation events and is oppositely regulated by Not1 and Not4, a mechanism that we additionally determine may already be set by Not1 promoter association in the nucleus.
Allen G.E., Weiss B., Panasenko O.O., Huch S., Villanyi Z., Albert B., Dilg D., Zagatti M., Schaughency P., Liao S.E., Corden J., Polte C., Shore D., Ignatova Z., Pelechano V., Collart M.A.
Not1 and Not4 inversely determine mRNA solubility that sets the dynamics of co-translational events
Abstract
In this work, by analyzing soluble and insoluble mRNA decay intermediates in yeast, we determine that insoluble mRNAs are enriched for ribosomes dwelling at non-optimal codons compared to soluble mRNAs. mRNA decay is higher for soluble RNAs, but the proportion of co-translational degradation relative to the overall mRNA decay is higher for insoluble mRNAs. We show that depletion of two subunits of the Ccr4-Not complex, Not1 and Not4, inversely impacts mRNA solubilities and, for soluble mRNAs, ribosome dwelling according to codon optimality. Depletion of Not4 solubilizes mRNAs with lower non-optimal codon content and higher expression that are rendered insoluble by Not1 depletion. By contrast, depletion of Not1 solubilizes mitochondrial mRNAs, which are rendered insoluble upon Not4 depletion.