A General Framework for Interrogation of mRNA Stability Programs Identifies RNA-Binding Proteins that Govern Cancer Transcriptomes
| Autor: | Mark Lathrop, Rosamonde E. Banks, Madeleine Arseneault, Fadi Brimo, Shraddha Solanki, Cristina Storoz, Mehran Karimzadeh, Yasser Riazalhosseini, Alvis Brazma, Ghislaine Scelo, Pouria Jandaghi, Gabrielle Perron, Sidong Huang, Jörg Tost, Hamed S. Najafabadi, Andreas I. Papadakis, Simon Tanguay, Maryam Safisamghabadi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Transcription Genetic RNA Stability RNA-binding protein Computational biology Disease Biology General Biochemistry Genetics and Molecular Biology Transcriptome 03 medical and health sciences Neoplasms Gene expression medicine Humans Gene Carcinoma Renal Cell lcsh:QH301-705.5 Cell Proliferation Regulation of gene expression Messenger RNA Cell Cycle Cancer RNA-Binding Proteins medicine.disease Kidney Neoplasms Neoplasm Proteins Up-Regulation Gene Expression Regulation Neoplastic 030104 developmental biology lcsh:Biology (General) Protein Biosynthesis |
| Zdroj: | Cell Reports, Vol 23, Iss 6, Pp 1639-1650 (2018) |
| ISSN: | 2211-1247 |
| Popis: | 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. : Perron et al. develop a computational approach that models the functional activity of RBPs in individual cancer samples by monitoring their associated RNA stability programs. Applying this method to renal cell carcinoma transcriptomes, the authors identify RBPs that enhance cancer-associated pathways including hypoxia and cell cycle. Keywords: RNA-binding proteins, gene regulation, mRNA stability, renal cancer, regulatory networks, network modeling, MBNL2, PCBP2, ESRP2 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|