TY - JOUR T1 - An RNA-binding switch drives ribosome biogenesis and tumorigenesis downstream of RAS oncogene JF - bioRxiv DO - 10.1101/2021.12.16.472890 SP - 2021.12.16.472890 AU - Muhammad S. Azman AU - Martin Dodel AU - Federica Capraro AU - Rupert Faraway AU - Maria Dermit AU - Wanling Fan AU - Jernej Ule AU - Faraz K. Mardakheh Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/12/16/2021.12.16.472890.abstract N2 - Oncogenic RAS signaling reprograms gene expression through both transcriptional and post-transcriptional mechanisms. While transcriptional regulation downstream of RAS is relatively well-characterized, how RAS post-transcriptionally modulates gene expression to promote malignancy is unclear. Using quantitative RNA Interactome Capture analysis, we reveal that oncogenic RAS signaling reshapes the RNA-bound proteomic landscape of cancer cells, with a network of nuclear proteins centered around Nucleolin displaying enhanced RNA-binding activity. We show that Nucleolin is phosphorylated downstream of RAS, which increases its binding to pre-ribosomal-RNA (rRNA), boosts rRNA production, and promotes ribosome biogenesis. This Nucleolin-dependent enhancement of ribosome biogenesis is crucial for RAS-induced cancer cell proliferation, and can be targeted therapeutically to inhibit tumor growth. Our results reveal that oncogenic RAS signaling drives ribosome biogenesis by regulating the RNA-binding activity of Nucleolin, and highlights the crucial role of this process in RAS-mediated tumorigenesis.Competing Interest StatementThe authors have declared no competing interest. ER -