A General Framework for Interrogation of mRNA Stability Programs Identifies RNA-Binding Proteins that Govern Cancer Transcriptomes | Zendy

Gabrielle Perron | Zendy; Pouria Jandaghi | Zendy; Shraddha Solanki | Zendy; Maryam Safisamghabadi | Zendy; Cristina Storoz | Zendy; Mehran Karimzadeh | Zendy; Andreas I. Papadakis | Zendy; Madeleine Arseneault | Zendy; Ghislaine Scélo | Zendy; Rosamonde E. Banks | Zendy; Jörg Tost | Zendy; Mark Lathrop | Zendy; Simon Tanguay | Zendy; Alvis Brāzma | Zendy; Sidong Huang | Zendy; Fadi Brimo | Zendy; Hamed S. Najafabadi | Zendy; Yasser Riazalhosseini | Zendy

Open Access

A General Framework for Interrogation of mRNA Stability Programs Identifies RNA-Binding Proteins that Govern Cancer Transcriptomes

Author(s) -

Gabrielle Perron,

Pouria Jandaghi,

Shraddha Solanki,

Maryam Safisamghabadi,

Cristina Storoz,

Mehran Karimzadeh,

Andreas I. Papadakis,

Madeleine Arseneault,

Ghislaine Scélo,

Rosamonde E. Banks,

Jörg Tost,

Mark Lathrop,

Simon Tanguay,

Alvis Brāzma,

Sidong Huang,

Fadi Brimo,

Hamed S. Najafabadi,

Yasser Riazalhosseini

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.04.031

Subject(s) - transcriptome , rna binding protein , biology , gene expression , messenger rna , gene , computational biology , regulation of gene expression , cancer , genetics , microbiology and biotechnology

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.

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