PT  - JOURNAL ARTICLE
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
TI  - An RNA-binding switch drives ribosome biogenesis and tumorigenesis downstream of RAS oncogene
AID  - 10.1101/2021.12.16.472890
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.12.16.472890
4099  - http://biorxiv.org/content/early/2021/12/16/2021.12.16.472890.short
4100  - http://biorxiv.org/content/early/2021/12/16/2021.12.16.472890.full
AB  - 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.