Cell Reports
Volume 23, Issue 6, 8 May 2018, Pages 1639-1650
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Article
A General Framework for Interrogation of mRNA Stability Programs Identifies RNA-Binding Proteins that Govern Cancer Transcriptomes

https://doi.org/10.1016/j.celrep.2018.04.031Get rights and content
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Highlights

  • Computational modeling of mRNA stability programs suggests a role of RBPs in cancer

  • Dysregulation of these programs leads to perturbation of cancer-associated pathways

  • RBP modulation in cell lines partially mirrors the transcriptome remodelling in cancer

Summary

Widespread remodeling of the transcriptome is a signature of cancer; however, little is known about the post-transcriptional regulatory factors, including RNA-binding proteins (RBPs) that regulate mRNA stability, and the extent to which RBPs contribute to cancer-associated pathways. Here, by modeling the global change in gene expression based on the effect of sequence-specific RBPs on mRNA stability, we show that RBP-mediated stability programs are recurrently deregulated in cancerous tissues. Particularly, we uncovered several RBPs that contribute to the abnormal transcriptome of renal cell carcinoma (RCC), including PCBP2, ESRP2, and MBNL2. Modulation of these proteins in cancer cell lines alters the expression of pathways that are central to the disease and highlights RBPs as driving master regulators of RCC transcriptome. This study presents a framework for the screening of RBP activities based on computational modeling of mRNA stability programs in cancer and highlights the role of post-transcriptional gene dysregulation in RCC.

Keywords

RNA-binding proteins
gene regulation
mRNA stability
renal cancer
regulatory networks
network modeling
MBNL2
PCBP2
ESRP2

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11

These authors contributed equally

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