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Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells

Dermit, M; Dodel, M; Lee, FCY; Azman, MS; Schwenzer, H; Jones, JL; Blagden, SP; ... Mardakheh, FK; + view all (2020) Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells. Developmental Cell , 55 (3) 298-313.e10. 10.1016/j.devcel.2020.10.006. Green open access

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Abstract

Translation of ribosomal protein-coding mRNAs (RP-mRNAs) constitutes a key step in ribosome biogenesis, but the mechanisms that modulate RP-mRNA translation in coordination with other cellular processes are poorly defined. Here, we show that subcellular localization of RP-mRNAs acts as a key regulator of their translation during cell migration. As cells migrate into their surroundings, RP-mRNAs localize to the actin-rich cell protrusions. This localization is mediated by La-related protein 6 (LARP6), an RNA-binding protein that is enriched in protrusions. Protrusions act as hotspots of translation for RP-mRNAs, enhancing RP synthesis, ribosome biogenesis, and the overall protein synthesis in migratory cells. In human breast carcinomas, epithelial-to-mesenchymal transition (EMT) upregulates LARP6 expression to enhance protein synthesis and support invasive growth. Our findings reveal LARP6-mediated mRNA localization as a key regulator of ribosome biogenesis during cell migration and demonstrate a role for this process in cancer progression downstream of EMT.

Type: Article
Title: Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.devcel.2020.10.006
Publisher version: https://doi.org/10.1016/j.devcel.2020.10.006
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: EMT, LARP6, La-related proteins, RNA localization, cancer, invasion, protrusion, ribosomal proteins, ribosome biogenesis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10115711
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