Pluto Bioinformatics

GSE71924: RNA-seq analysis of acute Rb1 deletion in adult mouse tissues

Bulk RNA sequencing

Abstract:The pRb tumor suppressor protein associates with chromatin and regulates gene expression. Numerous studies have identified Rb-dependent RNA signatures, but the proteomic effects of Rb-loss are largely unexplored. We have acutely ablated Rb in adult mice and conducted quantitative analysis of RNA and proteomic changes in colon and lung, where Rb-loss was sufficient or insufficient to induce ectopic proliferation respectively. As expected, RbKO caused similar increases in classic pRb/E2F-regulated transcripts in both tissues, but unexpectedly their protein products increased only in the colon, consistent with its increased proliferative index. Thus, these protein changes induced by Rb-loss are coupled with proliferation, but uncoupled from transcription. The proteomic changes in common between RbKO tissues showed a striking decrease in proteins with mitochondrial functions. Accordingly, RB1 inactivation in human cells decreased both mitochondrial mass and OXPHOS function. RBKO cells showed decreased mitochondrial respiratory capacity and the accumulation of hypopolarized mitochondria. Additionally, RB/Rb-loss altered mitochondrial pyruvate oxidation from 13C-Glucose through the TCA cycle in both cells and mouse tissues. Consequently, RBKO cells have an enhanced sensitivity to mitochondrial stress conditions. In summary, proteomic analyses provide a new perspective on Rb/RB1 mutation, highlighting the importance of pRb for mitochondrial function and suggesting vulnerabilities for treatment. SOURCE: Robert Morris ( - Mass. General Hospital Cancer Center

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