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bioRxiv · 10.1101/829739

Subcellular mRNA localization regulates ribosome biogenesis in migrating cells

Dermit, M.·Dodel, M.·Lee, F. C. Y.·Azman, M. S.·Schwenzer, H.·Jones, J. L.·Blagden, S. P.·Ule, J.·Mardakheh, F. K.
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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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Dermit, M., Dodel, M., Lee, F. C. Y., Azman, M. S., Schwenzer, H., Jones, J. L., Blagden, S. P., Ule, J., Mardakheh, F. K.. 2019-11-04. Subcellular mRNA localization regulates ribosome biogenesis in migrating cells. https://doi.org/10.1101/829739

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