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PreprintCited by 96RNA and protein synthesis mechanismsRNA Research and SplicingPI3K/AKT/mTOR signaling in cancer

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Subcellular mRNA localization regulates ribosome biogenesis in migrating cells

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Dermit, Maria, Dodel, Martin, Lee, Flora C. Y., Azman, Muhammad S., Schwenzer, Hagen, Jones, J. Louise, Blagden, Sarah P., Ule, Jernej, Mardakheh, Faraz K.·2019·Developmental Cell
DOI 10.1101/829739PMC PMC7660134

Preprint — published as 10.1016/j.devcel.2020.10.006

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Abstract

Translation of Ribosomal Protein-coding mRNAs (RP-mRNAs) constitutes a key step in ribosome biogenesis, but the mechanisms which modulate RP-mRNAs translation in coordination with other cellular processes are poorly defined. Here we show that the 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 actin-rich protrusions at the front the cells. 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, resulting in enhancement of ribosome biogenesis and overall protein synthesis, which is required for sustained migration. In human breast carcinomas, Epithelial to Mesenchymal Transition (EMT) upregulates LARP6 expression to enhance ribosome biogenesis 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.

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Metadata

Authors
Dermit, M., Dodel, M., Lee, F. C. Y., Azman, M. S., Schwenzer, H., Jones, J. L., Blagden, S. P., Ule, J., & Mardakheh, F. K.
Affiliations
  • Queen Mary University of London (GB)
  • The Francis Crick Institute (GB)
  • University of Oxford (GB)
Corresponding author
Mardakheh, Faraz K.
ORCID
Venue
Developmental Cell
Publisher
openRxiv
Published
2019-11-04
Volume
55
Issue
3
Pages
298-313.e10
ISSN
1534-5807 (ISSN-L)
DOI
10.1101/829739
PMC
PMC7660134
OpenAlex
W3103929311
Cited by
96
References
1
Citations by year
2026: 14 · 2025: 18 · 2024: 15 · 2023: 17 · 2022: 13 · 2021: 15 · 2020: 4
FWCI
4.22
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Developmental Cell (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UEA Digital Repository (University of East Anglia) (acceptedVersion, cc-by)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
Funders
  • Francis Crick Institute (10002)
  • Barts Charity (MGU0346)
  • Cancer Research UK (22598)
  • European Commission
  • Medical Research Council (MR/P009417/1, MR/P009417, MGU0346)
  • European Research Council (617837)
  • Seventh Framework Programme
  • H2020 European Research Council (617837)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
ribosome biogenesis, ribosomal protein mRNAs, mRNA localization, cell migration, LARP6, RNA-binding proteins, translational regulation, epithelial-mesenchymal transition, breast cancer, tumor progression, protein synthesis
MeSH terms
SS-B Antigen, Autoantigens, Organelle Biogenesis, Cell Movement, Humans, Neoplasms, Protein Binding, Ribonucleoproteins, Ribosomal Proteins, Ribosomes, RNA, Messenger, Subcellular Fractions, Protein Biosynthesis, Cell Surface Extensions, RNA Transport, Cell Proliferation, Epithelial-Mesenchymal Transition, Transcriptome

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