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

Cell Rep. 2018 May 8;23(6):1639-1650. doi: 10.1016/j.celrep.2018.04.031.


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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / genetics
  • Cell Cycle / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms / genetics*
  • Protein Biosynthesis
  • RNA Stability / genetics*
  • RNA-Binding Proteins / metabolism*
  • Transcription, Genetic
  • Transcriptome / genetics*
  • Up-Regulation / genetics


  • Neoplasm Proteins
  • RNA-Binding Proteins