New Tool Predicts How Proteins Interact with RNA Structures

Scientists at the Italian Institute of Technology and Aarhus University have figured out how specific proteins can bind to G-quadruplexes, which are unique RNA structures. They have also created computational tools that can forecast these interactions between RNA and protein.

Circular dichroism showing folding of RNA into G-quadruplexes at different temperatures. Image Credit: Luige et al. 2024

The ability to anticipate these interactions can aid in the future investigation of cellular molecular pathways and open the door to developing medications that specifically target the RNA G-quadruplex binding proteins linked to diseases like cancer.

Proteins that bind to RNA are involved in numerous cellular processes and can mediate a variety of biological functions. The G-quadruplex, a specialized structure found in both DNA and RNA, serves as a regulatory element influencing gene expression in both types of genetic material.

In the current study, the researchers demonstrated that numerous chromatin-binding proteins bind to RNA G-quadruplexes using molecular biology experiments and theoretical predictions. They can categorize proteins according to their ability to bind RNA G-quadruplexes using this information.

The goal of the study is to develop a prediction tool that indicates the likelihood of a protein binding to RNA G-quadruplexes by combining computational techniques with experimental methods for RNA G-quadruplex-binding protein identification.  The results indicate a high degree of hydrophilicity and protein disorder in the predicted proteins, which may be involved in phase-separation into membrane-less organelles and transcription.

Previously, Ulf Ørom's group demonstrated that RNA-DNA dual binding proteins likely play a role in the DNA damage response, connecting the binding properties of both DNA and RNA to various proteins. In their latest study, the researchers furthered their understanding of RNA-binding proteins by identifying proteins that bind to RNA G-quadruplexes.

The researchers have additionally created a computational tool designed to evaluate the potential of proteins to bind to RNA G-quadruplexes.

These new findings help the researchers understand the characteristics of protein-RNA interactions and offer a way to pinpoint the characteristics of G-quadruplex binding that may be used therapeutically to treat disease.

Source:
Journal reference:

Luige, J., et al. (2024) Predicting nuclear G-quadruplex RNA-binding proteins with roles in transcription and phase separation. Nature Communications. doi.org/10.1038/s41467-024-46731-9

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