Journal
NUCLEIC ACIDS RESEARCH
Volume 50, Issue 20, Pages 11426-11441Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkac950
Keywords
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Funding
- Israel Cancer Association [20221519]
- Israel Science Foundation [135/16, 3497/21, 424/22, 358/21, 425/22]
- Israeli Council for Higher Education (CHE) via Data Science Research Center, Ben-Gurion University of the Negev, Israel
- Andrea L. and Lawrence A. Wolfe Family Center for Research on Neuroimmunology and Neuromodulation
- CReATe consortium and ALSA
- RADALA Foundation
- AFM Telethon [20576]
- Weizmann-Brazil Center for Research on Neurodegeneration at Weizmann Institute of Science
- Minerva Foundation
- Federal German Ministry for Education and Research
- ISF Legacy Heritage Fund [828/17]
- Target ALS [118945]
- Thierry Latran Foundation for ALS Research
- European Research Council under the European Union [617351]
- United States-Israel Binational Science Foundation [2021181]
- ERA-Net for Research Programs on Rare Diseases [eRARE FP7] via the Israel Ministry of Health
- Israel Ministry of Trade and Industry
- Y. Leon Benoziyo Institute for Molecular Medicine
- Nella and Leon Benoziyo Center for Neurological Diseases
- Kekst Family Institute for Medical Genetics
- David and Fela Shapell Family Center for Genetic Disorders Research
- Crown Human Genome Center
- Nathan, Shirley, Philip and Charlene Vener New Scientist Fund
- Julius and Ray Charlestein Foundation
- Fraida Foundation
- Wolfson Family Charitable Trust
- Adelis Foundation
- Merck (UK)
- Goldhirsh-Yellin Foundation
- Redhill Foundation-Sam and Jean Rothberg Charitable Trust
- Dr Dvora and Haim Teitelbaum Endowment Fund
- Anita James Rosen Foundation
- CNRS-WIS center for research of RNA secondary structures
- Direct For Biological Sciences
- Division Of Environmental Biology [2021181] Funding Source: National Science Foundation
- European Research Council (ERC) [617351] Funding Source: European Research Council (ERC)
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RNA G-quadruplexes (rG4s) play a direct role in stress granule (SG) biology through their interactions with RNA-binding proteins. The newly developed rG4detector is a powerful tool for predicting and detecting rG4 stability and forming sequences in transcriptomics data.
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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