1-s2.0-S1534580720307966-main (1).pdf (6.57 MB)
Subcellular mRNA localization regulates ribosome biogenesis in migrating cells.
journal contributionposted on 2020-11-19, 09:33 authored by Maria Dermit, Martin Dodel, Flora CY Lee, Muhammad S Azman, Hagen Schwenzer, J Louise Jones, Sarah P Blagden, Jernej Ule, Faraz K Mardakheh
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.
Crick (Grant ID: 10002, Grant title: Ule FC001002)