4.8 Article

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

期刊

CELL REPORTS
卷 32, 期 8, 页码 -

出版社

CELL PRESS
DOI: 10.1016/j.celrep.2020.108064

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资金

  1. Marshall Plan Foundation
  2. Austrian Federal Ministry for Education
  3. National Institutes of Health (NIH) [R01ES015339, R35-ES028374, R01-CA226898, U54-CA112967]
  4. Charles and Marjorie Holloway Foundation
  5. MIT Center for Precision Cancer Medicine
  6. Starr Cancer Consortium [I9-A9-077]
  7. Koch Institute Support (core) Grant from the National Cancer Institute [P30-CA14051]

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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.

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