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Article Dans Une Revue Nucleic Acids Research Année : 2022

rG4detector, a novel RNA G-quadruplex predictor, uncovers their impact on stress granule formation

Maor Turner
  • Fonction : Auteur
Yehuda M Danino
Mira Barshai
  • Fonction : Auteur
Nancy S Yacovzada
  • Fonction : Auteur
Yahel Cohen
  • Fonction : Auteur
Tsviya Olender
  • Fonction : Auteur
Ron Rotkopf
Eran Hornstein
  • Fonction : Auteur
Yaron Orenstein

Résumé

Abstract RNA G-quadruplexes (rG4s) are RNA secondary structures, which are formed by guanine-rich sequences and have important cellular functions. Existing computational tools for rG4 prediction rely on specific sequence features and/or were trained on small datasets, without considering rG4 stability information, and are therefore sub-optimal. Here, we developed rG4detector, a convolutional neural network to identify potential rG4s in transcriptomics data. rG4detector outperforms existing methods in both predicting rG4 stability and in detecting rG4-forming sequences. To demonstrate the biological-relevance of rG4detector, we employed it to study RNAs that are bound by the RNA-binding protein G3BP1. G3BP1 is central to the induction of stress granules (SGs), which are cytoplasmic biomolecular condensates that form in response to a variety of cellular stresses. Unexpectedly, rG4detector revealed a dynamic enrichment of rG4s bound by G3BP1 in response to cellular stress. In addition, we experimentally characterized G3BP1 cross-talk with rG4s, demonstrating that G3BP1 is a bona fide rG4-binding protein and that endogenous rG4s are enriched within SGs. Furthermore, we found that reduced rG4 availability impairs SG formation. Hence, we conclude that rG4s play a direct role in SG biology via their interactions with RNA-binding proteins and that rG4detector is a novel useful tool for rG4 transcriptomics data analyses.
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Dates et versions

hal-03852407 , version 1 (15-11-2022)
hal-03852407 , version 2 (17-01-2023)

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Maor Turner, Yehuda M Danino, Mira Barshai, Nancy S Yacovzada, Yahel Cohen, et al.. rG4detector, a novel RNA G-quadruplex predictor, uncovers their impact on stress granule formation. Nucleic Acids Research, 2022, ⟨10.1093/nar/gkac950⟩. ⟨hal-03852407v1⟩
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