Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells

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 regulat...

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Bibliographic Details
Published in:Developmental cell 2020-11, Vol.55 (3), p.298-313.e10
Main Authors: Dermit, Maria, Dodel, Martin, Lee, Flora C Y, Azman, Muhammad S, Schwenzer, Hagen, Jones, J Louise, Blagden, Sarah P, Ule, Jernej, Mardakheh, Faraz K
Format: Article
Language:English
Subjects:
Autoantigens - metabolism
Cell Movement
Cell Proliferation
Cell Surface Extensions - metabolism
Epithelial-Mesenchymal Transition
Humans
Neoplasms - metabolism
Neoplasms - pathology
Organelle Biogenesis
Protein Binding
Protein Biosynthesis
Ribonucleoproteins - metabolism
Ribosomal Proteins - metabolism
Ribosomes - metabolism
RNA Transport
RNA, Messenger - genetics
RNA, Messenger - metabolism
SS-B Antigen
Subcellular Fractions - metabolism
Transcriptome - genetics
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Summary: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.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2020.10.006