Transite: A Computational Motif-Based Analysis Platform That Identifies RNA-Binding Proteins Modulating Changes in Gene Expression

Konstantin Krismer, Molly A. Bird, Shohreh Varmeh, Erika D. Handly, Anna Gattinger, Thomas Bernwinkler, Daniel A. Anderson, Andreas Heinzel, Brian A. Joughin, Yi Wen Kong, Ian G. Cannell, Michael B. Yaffe

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

RNA-binding proteins (RBPs) play critical roles in regulating gene expression by modulating splicing, RNA stability, and protein translation. Stimulus-induced alterations in RBP function contribute to global changes in gene expression, but identifying which RBPs are responsible for the observed changes remains an unmet need. Here, we present Transite, a computational approach that systematically infers RBPs influencing gene expression through changes in RNA stability and degradation. As a proof of principle, we apply Transite to RNA expression data from human patients with non-small-cell lung cancer whose tumors were sampled at diagnosis or after recurrence following treatment with platinum-based chemotherapy. Transite implicates known RBP regulators of the DNA damage response and identifies hnRNPC as a new modulator of chemotherapeutic resistance, which we subsequently validated experimentally. Transite serves as a framework for the identification of RBPs that drive cell-state transitions and adds additional value to the vast collection of publicly available gene expression datasets.

Original languageEnglish
Article number108064
Pages (from-to)108064
JournalCell Reports
Volume32
Issue number8
DOIs
Publication statusPublished - 25 Aug 2020

Keywords

  • chemotherapy
  • DNA damage response
  • post-transcriptional regulation
  • RNA-binding proteins
  • sequence motifs
  • RNA-Binding Proteins/metabolism
  • DNA Damage/genetics
  • Humans
  • Gene Expression/genetics

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