Researchers from Aarhus University and the Italian Institute of Technology have made a groundbreaking discovery regarding how certain proteins can attach to special structures in RNA known as G-quadruplexes. Moreover, they have devised computational tools capable of predicting these protein-RNA interactions. This newfound ability to forecast interactions could potentially assist in comprehending molecular pathways in the cell and serve as a stepping stone for the development of drugs targeting these RNA G-quadruplex binding proteins, which have been linked to diseases such as cancer.
Proteins that bind to RNA play crucial roles in numerous processes within the cell and can facilitate a variety of biological functions. The G-quadruplex, a specialized structure present in both DNA and RNA, serves as a regulatory element involved in gene expression in both types of nucleic acids. The researchers in this study utilized theoretical predictions and molecular biology experiments to demonstrate that many chromatin-binding proteins have the ability to bind to RNA G-quadruplexes. With this knowledge, they can categorize proteins based on their potential to interact with RNA G-quadruplexes.
By combining experimental identification of RNA G-quadruplex-binding proteins with computational methods, the study generated a prediction tool capable of assessing the likelihood that a protein binds to RNA G-quadruplexes. The results reveal that the proteins predicted to bind to RNA G-quadruplexes exhibit a high degree of protein disorder and hydrophilicity, indicating potential involvement in transcription and phase-separation into membrane-less organelles. This sheds light on the roles of these proteins in cellular processes.
Previously, Ulf Ørom’s group had demonstrated that RNA-DNA dual binding proteins likely play a role in the DNA damage response, connecting DNA and RNA binding properties of numerous proteins. In this new study, the researchers further expanded their understanding of RNA-binding proteins by identifying RNA G-quadruplex binding proteins. This enriches the knowledge base regarding the interactions between proteins and RNA.
Additionally, the researchers have developed a computational tool to evaluate the RNA G-quadruplex-binding potential of proteins, which is accessible at a specific website. These findings provide insights into the properties of protein-RNA interactions and offer a means to identify G-quadruplex binding properties that could potentially be targeted therapeutically in diseases. The significance of these results has been highlighted by their publication in Nature Communications, underscoring their contribution to the field of RNA research and potential implications for disease treatment strategies.
