Subcellular mRNA localization regulates ribosome biogenesis in migrating cells
Institution: Barts Cancer Institute, Queen Mary University of London
Corresponding Researcher: Faraz Mardakheh
Data Link(s): The mass spectrometry raw files and their associated MaxQuant output files generated during this study are available at ProteomeXchange Consortium via the PRIDE partner repository (http://www.ebi.ac.uk/pride/archive/), as listed in the Key Resources Table. In addition, all RNA-sequencing FASTQ files generated during this study are available at ArrayExpress database (http://www.ebi.ac.uk/arrayexpress), as listed in the Key Resources Table. The accesssion numbers for the mass spectrometry datasets reported in this paper are PRIDE: PXD021203, PXD021204, PXD021205, PXD021206, PXD021239, and PXD021180. The accesssion numbers for the RNA-sequencing datasets reported in this paper are ArrayExpress: E-MTAB-8470, E-MTAB-9520, and E-MTAB-9636.
Keyword(s): IHC, RNA localization, ribosome biogenesis, La-related proteins, EMT, LARP6
Summary
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.
