Subcytoplasmic location of translation controls protein output

The cytoplasm is highly compartmentalized, but the extent of subcytopIasmic mRNA localization in non-polarized cells is largely unknown. We used fluorescent particle sorting to determine mRNA enrichment in three unenclosed cytoplasmic compartments: the canonicaI rough endopIasmic reticuIum (CRER), the TIS granule-associated rough endopIasmic reticuIum (TGER), and the cytosol. Focusing our analysis on non-membrane protein-encoding mRNAs, we observed that 53% have a unique subcytoplasmic localization pattern which is determined by a combinatorial code of 3′UTR-bound RNA-binding proteins. Compartment-enriched mRNAs differed in production and degradation rates and the expression levels and functional classes of their encoded proteins. The TGER domain enriches mRNAs that encode transcription factors, the CRER highly expressed proteins, and the cytosol unstable mRNAs. The rough ER environment is stimulatory as redirecting cytosolic mRNAs to the ER increases their protein expression by two-fold, independently of the bound RNA-binding proteins. We show that local translation environments functionally compartmentaIize the cytoplasm.