A Localization Screen Reveals Translation Factories and Widespread Co-Translational Protein Targeting
2018
Local translation allows a spatial control of gene expression. Here, we performed a dual protein/mRNA localization screen, using smFISH on 521 human cell lines expressing GFPtagged genes. A total of 32 mRNAs displayed specific cytoplasmic localizations, and we observed local translation at unexpected locations, including cytoplasmic protrusions, cell edges, endosomes, Golgi, the nuclear envelope and centrosomes, the latter being cell-cycle dependent. Surprisingly, mRNA localization frequently required ongoing translation, indicating widespread co-translational targeting. Nevertheless, the kinesin KIF1C localized mRNAs to cytoplasmic protrusions in a translation-independent manner. Interestingly, while P-body accumulation was frequent (15 mRNAs), four mRNAs accumulated in foci that were distinct structures. These foci lacked the mature protein, but nascent polypeptide imaging showed that they were specialized translation factories. For β-catenin, foci formation was regulated by Wnt, relied on APCdependent polysome aggregation, and led to nascent protein degradation. Thus, translation factories uniquely regulate nascent protein metabolism and create a fine granular compartmentalization of translation.
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