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Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells
Maria Dermit1, Martin Dodel1, Flora C Y Lee2
1Centre for Cancer Cell and Molecular Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Developmental Cell
|November 10, 2020
Summary
Cell migration directs ribosomal protein mRNA (RP-mRNA) to protrusions, boosting protein synthesis. La-related protein 6 (LARP6) mediates this, impacting cell migration and cancer progression.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Ribosome biogenesis is crucial for cell function.
- Mechanisms regulating translation of ribosomal protein mRNAs (RP-mRNAs) during cell migration are not well understood.
Purpose of the Study:
- To investigate the role of subcellular mRNA localization in regulating RP-mRNA translation during cell migration.
- To identify the protein factors involved in this process.
Main Methods:
- Studied RP-mRNA localization in migrating cells.
- Investigated the function of La-related protein 6 (LARP6) in mRNA localization and translation.
- Analyzed LARP6 expression in human breast cancer tissues and its correlation with epithelial-to-mesenchymal transition (EMT).
Main Results:
- RP-mRNAs were found to localize to actin-rich cell protrusions during migration.
- LARP6 was identified as the RNA-binding protein responsible for this localization.
- Localized RP-mRNAs in protrusions served as translation hotspots, enhancing protein synthesis in migratory cells.
- EMT in breast cancer upregulated LARP6, promoting protein synthesis and invasive growth.
Conclusions:
- LARP6-mediated RP-mRNA localization to cell protrusions is a key regulator of ribosome biogenesis during cell migration.
- This mechanism plays a significant role in cancer progression, particularly downstream of EMT.
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