RT Journal Article
SR Electronic
T1 An RNA-binding switch drives ribosome biogenesis and tumorigenesis downstream of RAS oncogene
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.12.16.472890
DO 10.1101/2021.12.16.472890
A1 Muhammad S. Azman
A1 Martin Dodel
A1 Federica Capraro
A1 Rupert Faraway
A1 Maria Dermit
A1 Wanling Fan
A1 Jernej Ule
A1 Faraz K. Mardakheh
YR 2021
UL http://biorxiv.org/content/early/2021/12/16/2021.12.16.472890.abstract
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.