Fig. 7

Model for the opposing regulation of mRNA solubility by Not1 and Not4. mRNAs exhibit diverse solubilities, and mRNAs that are not soluble can be either in functional condensates, associated with membranes, or in cytosolic aggregates. Not1 and Not4 have opposing effects on mRNA solubility and solubility of some mRNAs (designated red) is promoted by Not1, whereas for another set (green), solubility is promoted by Not4. mRNAs that are less soluble upon Not1 depletion but more upon Not4 depletion (red) are transcribed from genes with high Not1 recruited at their promoters. Not4, also co-transcriptionally recruited to mRNAs, opposes their solubilization. These mRNAs have low non-optimal codon content and are highly expressed. They show high Not1 binding in not5Δ (RIP) background and Not4 cross-linking is lower compared to the mRNAs that instead are less soluble upon Not4 depletion but more upon Not1 depletion (green mRNAs). These latter mRNAs are generally more soluble and they are less likely to have co-transcriptional recruitment of Not1. They remain soluble in a Not4-dependent manner. Solubility of these mRNAs is compromised by the depletion of Not4, possibly because Not1 recruitment is thereby enabled, since depletion of Not1 instead increases their solubility. Note that Not1 and Not4 are placed on mRNAs to indicate functional interaction, but do not infer direct mRNA binding