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

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.

• Authors: 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
• Journal: Cell reports (Cell Rep) Vol. 32 Issue 8 Pg. 108064 (08 25 2020) ISSN: 2211-1247 [Electronic] United States
• PMID: 32846122 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• RNA-Binding Proteins

Topics

• DNA Damage (genetics)
• Gene Expression (genetics)
• Humans
• RNA-Binding Proteins (metabolism)