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

Abstract

SUMMARY 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.

Liver Transcriptome Dynamics During Hibernation Are Shaped by a Shifting Balance Between Transcription and RNA Stability

“…Sequence analyses were carried out in R, utilizing a forged BSgenome data package from the newly built genome assembly (Fu et al, 2021), which enables quick queries of untranslated sequences. In addition, k-mer counting and enrichment statistical analysis are achieved through the R package transite (Krismer et al, 2020).…”

Members of the CUGBP Elav-Like Family of RNA-Binding Proteins are Expressed in Distinct Populations of Primary Sensory Neurons

“…Previous studies examining the expression profile and function of CELF members have determined that these proteins are expressed in the central nervous system during development and in the adult (Table 4 (Giudice et al, 2016;Krismer et al, 2020b;Samaras et al, 2020;Schmidt et al, 2018)). The RNA-binding motifs for all members are similar, with UG repeats (Table 4), suggesting that these proteins have the ability to bind similar transcripts.…”

Microglia perform local protein synthesis at perisynaptic and phagocytic structures

“…RBP motifs were identified by entering transcript lists into the Transite transcript set motif analysis online tool (transite.mit.edu) 29 . We separately analyzed the 5’ and 3’ UTRs of PeMP and Somal gene lists using a matrix-based analysis, with the full MG-TRAP list as the background.…”

“…In neurons and many other cell types, RNA binding proteins (RBPs) bind to defined sequence motifs largely within UTRs to regulate mRNA localization, stability, and or degradation. We then utilized the Transite set motif analysis tool 29 to test for differential RBP motif usage in the 3' and 5' UTRs of PeMP and somal localized microglial transcripts, focusing on motifs that showed the greatest difference in representation between those two groups ( Extended Data 5 ). As motifs are often similar across RBPs, we followed this with hierarchical clustering to group similar motifs ( Fig.…”

“…Similar GO terms were grouped with the most significant term displayed within a tree of minimum 2 common and maximum 4 different parents. Groupings are indicated by a shared color on the force directed nodal networks( Figure 3a-b) and in Extended Data 4.The nodal network graphic for PeMP-enriched transcripts was restricted to p < 0.02.RBP motif discovery using Transite transcript set motif analysisRBP motifs were identified by entering transcript lists into the Transite transcript set motif analysis online tool (transite.mit.edu)29 . We separately analyzed the 5' and 3' UTRs of PeMP and Somal gene lists using a matrix-based analysis, with the full MG-TRAP list as the background.…”