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Updated: Feb 21, 2026

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A deep learning framework for comprehensive prediction of human RNA G-quadruplex-binding proteins.

Serena Rosignoli1, Sophie Taraglio2, Francesco Di Luzio3

  • 1Centre for Regenerative Medicine "Stefano Ferrari", Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41125, Italy.

Bioinformatics (Oxford, England)
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We developed a deep learning model to predict RNA G-quadruplex-binding proteins (RG4BPs), crucial for RNA metabolism and stress. This tool identified thousands of new RG4BP candidates, advancing RNA regulation research.

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Area of Science:

  • Computational Biology
  • Molecular Biology
  • Bioinformatics

Background:

  • G-quadruplex-binding proteins (G4BPs) are vital for RNA metabolism and cellular stress responses.
  • Experimental identification of G4BPs is challenging, necessitating computational approaches.

Purpose of the Study:

  • To develop and validate a deep learning framework for predicting RNA G4BPs (RG4BPs).
  • To identify novel RG4BP candidates within the human proteome.
  • To provide a user-friendly web server for RG4BP prediction and analysis.

Main Methods:

  • Integration of diverse encoding strategies and neural architectures, including ESM-2 protein language model embeddings and an LSTM architecture.
  • Application of the trained model to the human proteome for candidate identification.
  • Development of the G4REP web server for accessible RG4BP prediction.

Main Results:

  • The best-performing deep learning model achieved 86% accuracy in identifying RG4BPs.
  • Identified 2,160 high-confidence RG4BP candidates in the human proteome.
  • Discovered that many RG4BP candidates possess intrinsically disordered regions and are enriched in stress granules, suggesting a link to cellular stress.

Conclusions:

  • The study provides an effective computational approach to explore the landscape of RG4BPs.
  • Novel RG4BP candidates and their potential roles in RNA regulation and stress response pathways were uncovered.
  • The G4REP web server facilitates broad access to RG4BP prediction and analysis tools.