Subcellular mRNA Localization Regulates Ribosome Biogenesis In Migrating Cells
44 Pages Posted: 28 Jan 2020 Sneak Peek Status: Under ReviewMore...
Translation of Ribosomal Protein-coding mRNAs (RP-mRNAs) constitutes a key step in ribosome biogenesis, but the mechanisms which modulate RP-mRNA 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 the actin-rich protrusive fronts of 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 RP synthesis, ribosome biogenesis, and overall protein synthetic capacity of migratory cells, required for supporting efficient migration and proliferation. 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.
Keywords: RNA localization, local translation, ribosome biogenesis, mTORC1, LARP1, LARP6, translation, Cell Migration, invasion, EMT
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