Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells

Abstract

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.

Purification and quantitative proteomic analysis of cell bodies and protrusions

“…For other methods based on chemotactic stimulation please see ( Mili et al., 2008 ). Optional: Different incubation times may be used, which may give a different protrusion proteome profiles as we showed in Dermit et al. (2020) .…”

“…Optional: Different incubation times may be used, which may give a different protrusion proteome profiles as we showed in Dermit et al. (2020) .…”

“…This protocol enables purification, quantification, and analysis of the distribution of proteins present in protrusions and cell bodies. For complete details on the use and execution of this protocol, please refer to Dermit et al. (2020) .…”

“…For complete details on the use and execution of this protocol, please refer to Dermit et al. (2020) .…”

Exploration and Verification of a Six-RNA Binding Proteins-based Prognosis Evaluating Model for Hepatocellular Carcinoma

“…domains and double-stranded RNA-binding domain, etc. Existing articles have proved that RBPs take part in various biological processes, like splicing of the RNA [8], subcellular localization of mRNA [9], translation and m6A modi cation [10] of RNA, stabilizing of target RNA [11]. Considering the dysfunction of RBPs may disturb the balance of transcription or translation process and therefore induces tumorigenesis, the role of RBPs in malignant disease were investigated by researchers.…”