Transite: A computational motif-based analysis platform that identifies RNA-binding proteins modulating changes in gene expression

RNA-binding proteins (RBPs) play critical roles in regulating gene expression by modulating splicing, RNA stability, and protein translation and are frequently the targets of signal transduction pathways that control RBP function through post-translational modifications such as phosphorylation. In response to various stimuli, alterations in RBP function contribute to global changes in gene expression, but identifying which specific RNA-binding protein(s) are responsible for the observed changes in gene expression patterns remains an unmet need. Here, we present Transite - a computational approach to systematically infer RBPs influencing gene expression changes through alterations in RNA stability and degradation. Specifically, our approach builds on pre-existing differential gene expression data and performs sequence-based enrichment analysis. By matching the enriched sequences to a compendium of RBP-binding motifs, we can identify potential RBPs responsible for the observed gene expression changes. As an example, we applied Transite to examine RBPs potentially involved in the response of human patients with non-small cell lung cancer to platinum-based chemotherapy, since RBPs have been recently identified as one of the primary classes of proteins influencing the DNA damage response. Transite implicated known RBP regulators of the DNA damage response and identified hnRNPC as a new modulator of chemotherapeutic resistance, which was subsequently validated experimentally. These data show that Transite is a generalizable framework for the identification of RBPs responsible for gene expression changes driving cell-state transitions and adds value to the vast wealth of publicly-available gene expression data. To ensure that Transite is available to a broad range of scientists for routine differential gene expression analysis workflows we have built a user-friendly web interface that is accessible at https://transite.mit.edu.