Subcytoplasmic location of translation controls protein output

Mol Cell. 2023 Dec 21;83(24):4509-4523.e11. doi: 10.1016/j.molcel.2023.11.025.


The cytoplasm is highly compartmentalized, but the extent and consequences of subcytoplasmic mRNA localization in non-polarized cells are largely unknown. We determined mRNA enrichment in TIS granules (TGs) and the rough endoplasmic reticulum (ER) through particle sorting and isolated cytosolic mRNAs by digitonin extraction. When focusing on genes that encode non-membrane proteins, we observed that 52% have transcripts enriched in specific compartments. Compartment enrichment correlates with a combinatorial code based on mRNA length, exon length, and 3' UTR-bound RNA-binding proteins. Compartment-biased mRNAs differ in the functional classes of their encoded proteins: TG-enriched mRNAs encode low-abundance proteins with strong enrichment of transcription factors, whereas ER-enriched mRNAs encode large and highly expressed proteins. Compartment localization is an important determinant of mRNA and protein abundance, which is supported by reporter experiments showing that redirecting cytosolic mRNAs to the ER increases their protein expression. In summary, the cytoplasm is functionally compartmentalized by local translation environments.

Keywords: 3′ UTR; CDS exon length; RNA-binding proteins; TIAL1; TIS granules; TIS11B; condensates; cytoplasmic organization; endoplasmic reticulum; gene architecture; mRNA length; mRNA localization; spatial regulation of protein synthesis; translation environment.

MeSH terms

  • Cytosol / metabolism
  • Endoplasmic Reticulum* / genetics
  • Endoplasmic Reticulum* / metabolism
  • Protein Biosynthesis
  • Protein Transport
  • Proteins* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Proteins
  • RNA, Messenger