Subcytoplasmic location of translation controls protein output

Abstract

SummaryThe 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 52% have a biased subcytoplasmic localization pattern which is determined by a combinatorial code of 3’UTR-bound RNA-binding proteins. Compartment-biased mRNAs differed in the functional classes of their encoded proteins. TGER-enriched mRNAs encode low-abundance proteins such as transcription factors, whereas CRER-enriched mRNAs encode highly expressed proteins. TGER/CRER-enriched mRNAs are more stable than cytosolic mRNAs, thus influencing protein output in a compartment-dependent manner. We observed that redirecting cytosolic mRNAs to the ER increases their protein expression by two-fold, independently of the bound RNA-binding proteins. In summary, the cytoplasm is functionally compartmentaIized by local translation environments.