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New tools reveal how genes work and cells organize

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Proteins binding to RNA are important in many processes in the cell and can mediate a range of biological functions. A specialized structure in both DNA and RNA, the G-quadruplex, are regulatory elements involved in gene expression in both DNA and RNA. In the present work the researchers use theoretical predictions and molecular biology experiments to show that many chromatin-binding proteins bind to RNA G-quadruplexes. With this information they can classify proteins based on their potential to bind RNA G-quadruplexes.

Credit: Luige et al. 2024

Proteins binding to RNA are important in many processes in the cell and can mediate a range of biological functions. A specialized structure in both DNA and RNA, the G-quadruplex, are regulatory elements involved in gene expression in both DNA and RNA. In the present work the researchers use theoretical predictions and molecular biology experiments to show that many chromatin-binding proteins bind to RNA G-quadruplexes. With this information they can classify proteins based on their potential to bind RNA G-quadruplexes.

The study uses a combination of experimental identification of RNA G-quadruplex-binding proteins and computational methods to build a prediction tool that identify the probability that a protein binds to RNA G-quadruplexes.  The findings show that predicted proteins show a high degree of protein disorder and hydrophilicity, suggesting an involvement in both transcription and phase-separation into membrane-less organelles.

Ulf Ørom’s group has previously shown that RNA-DNA dual binding proteins are likely to have an involvement in the DNA damage response, linking DNA and RNA binding properties to a number of proteins. In the new study, the researchers expanded the knowledge of RNA-binding proteins to identify RNA G-quadruplex binding proteins.  

The researchers have also developed a computational tool to assess RNA G-quadruplex-binding potential of proteins that can be accessed at http://service.tartaglialab.com/new_submission/clever_G4_classifier.

With these new results, the researchers identify properties of protein-RNA interactions, and provide means to identify G-quadruplex binding properties that can potentially be targeted therapeutically in disease.

The findings have just been published in Nature Communications.


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