Subcytoplasmic location of translation controls protein output
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Ellen L Horste Mervin M Fansler Ting Cai Xiuzhen Chen Sibylle Mitschka Gang Zhen Flora Lee Jernej Ule Christine MayrAbstract
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.
Journal details
Journal
Molecular Cell
Volume
83
Issue number
24
Pages
4509-4523.e11
Available online
Publication date
Full text links
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10.1016/j.molcel.2023.11.025
Europe PubMed Central
38134885
Pubmed
38134885
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The publication was previously a preprint.
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