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Updated: Feb 21, 2026

Capture and Identification of RNA-binding Proteins by Using Click Chemistry-assisted RNA-interactome Capture CARIC Strategy
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Capture and Identification of RNA-binding Proteins by Using Click Chemistry-assisted RNA-interactome Capture CARIC Strategy

Published on: October 19, 2018

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Mutational landscape of RNA-binding proteins in human cancers

Yaseswini Neelamraju1, Abel Gonzalez-Perez2, Poornima Bhat-Nakshatri3

  • 1a Department of Bio Health Informatics, School of Informatics and Computing , Indiana University Purdue University , Indianapolis , Indiana , USA.

RNA Biology
|October 13, 2017
PubMed

Insights

This study maps mutations in RNA Binding Proteins (RBPs) across thousands of cancer genomes, identifying key RBPs driving cancer and revealing their role in post-transcriptional regulation and tumor development.

Area of Science:

  • Genomics and Molecular Biology
  • Cancer Research
  • Post-transcriptional Regulation

Background:

  • RNA Binding Proteins (RBPs) are crucial for post-transcriptional gene regulation.
  • Dysfunctional RBPs are increasingly implicated in cancer genomes, but their specific roles are not fully understood.
  • A comprehensive analysis of RBP mutations in cancer is needed to elucidate their contribution to tumorigenesis.

Purpose of the Study:

  • To delineate the mutational landscape of approximately 1300 RBPs across nearly 6000 cancer genomes.
  • To identify cancer-specific RBP mutation hotspots and driver RBPs.
  • To investigate the functional impact of RBP mutations on cancer pathways and phenotypes.

Main Methods:

  • Analysis of mutational data from ∼6000 cancer genomes focusing on ∼1300 RBPs.
  • Identification of mutationally enriched RBPs (GEMs) and candidate driver RBPs using the OncodriveFM framework.
  • Functional enrichment analysis, network analysis, and gene knockdown experiments in cancer cell lines.

Main Results:

  • Identified 281 RBPs enriched for mutations (GEMs) across 26 cancer types, with frequent frameshift, deletion, and missense mutations.
  • Discovered over 200 candidate driver RBPs with functionally impactful mutations, affecting pathways like apoptosis, splicing, and translation.
  • Network analysis revealed altered protein interaction networks and cancer-specific RNP mutational hotspots; knockdown experiments showed RBPs mediate cancer-specific stem cell features.

Conclusions:

  • Mutations in RBPs are widespread in cancer and significantly impact post-transcriptional regulatory networks.
  • Specific driver RBPs and their mutational patterns offer potential therapeutic targets and insights into cancer heterogeneity.
  • This study provides a foundational understanding of the RBP mutational spectrum in cancer, paving the way for further investigation into their oncogenic roles.
Keywords:
Somatic mutationscancer genomicsgene regulatory networksoncogenespost-transcriptional regulation

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