A Dual Protein-mRNA Localization Screen Reveals Compartmentalized Translation and Widespread Co-translational RNA Targeting

Racha Chouaib (1, 2) , Adham Safieddine (1, 2) , Xavier Pichon (1) , Arthur Imbert (3, 4) , Oh Sung Kwon (5) , Aubin Samacoits (6, 7) , Abdel-Meneem Traboulsi (1) , Marie-Cécile Robert (1) , Nikolay Tsanov (1) , Emeline Coleno (1) , Ina Poser (8) , Christophe Zimmer (6, 7) , Anthony A. Hyman (8) , Hervé Le Hir (5) , Kazem Zibara (2) , Marion Peter (1) , Florian Mueller (6, 7) , Thomas Walter (3, 4) , Edouard Bertrand (1, 9)

1 IGMM - Institut de Génétique Moléculaire de Montpellier
2 ER045-PRASE - Laboratory of Stem Cells [Lebanese, Beirut]
3 CBIO - Centre de Bioinformatique
4 Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe
5 IBENS - Institut de biologie de l'ENS Paris
6 Imagerie et Modélisation - Imaging and Modeling
7 C3BI - Centre de Bioinformatique, Biostatistique et Biologie Intégrative
8 MPI-CBG - Max Planck Institute of Molecular Cell Biology and Genetics
9 Equipe labellisée Ligue contre le Cancer

Local translation allows spatial control of gene expression. Here, we performed a dual protein-mRNA localization screen, using smFISH on 523 human cell lines expressing GFP-tagged genes. 32 mRNAs displayed specific cytoplasmic localizations with local translation at unexpected locations, including cytoplasmic protrusions, cell edges, endosomes, Golgi, the nuclear envelope, and centrosomes, the latter being cell-cycle-dependent. Automated classification of mRNA localization patterns revealed a high degree of intercellular heterogeneity. Surprisingly, mRNA localization frequently required ongoing translation, indicating widespread co-translational RNA targeting. 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 APC-dependent polysome aggregation, and led to nascent protein degradation. Thus, translation factories uniquely regulate nascent protein metabolism and create a fine granular compartmentalization of translation.

Keywords: translation factories; smFISH; local translation; co-translational targeting; RNA transport; Beta-catenin; RNA localization; ASPM; co-translational targeting Manuscript

Domains: Subcellular Processes [q-bio.SC]

Racha Chouaib, Adham Safieddine, Xavier Pichon, Arthur Imbert, Oh Sung Kwon, et al.. A Dual Protein-mRNA Localization Screen Reveals Compartmentalized Translation and Widespread Co-translational RNA Targeting. Developmental Cell, 2020, 54 (6), pp.773 - 791.e5. ⟨10.1016/j.devcel.2020.07.010⟩. ⟨pasteur-02925687⟩