Predicting nuclear G-quadruplex RNA-binding proteins with roles in transcription and phase separation

Area of Science:

• Molecular Biology
• Biochemistry
• Genomics

Background:

• RNA-binding proteins (RBPs) are essential for diverse biological functions, interacting with various RNA structures.
• RNA G-quadruplexes (G4s) are regulatory elements in transcripts, but their structure-based interactions with proteins are not well understood.

Purpose of the Study:

• To identify and classify chromatin-binding proteins that interact with RNA G-quadruplexes.
• To develop a predictive tool for estimating the RNA G-quadruplex-binding potential of nuclear proteins.
• To investigate the biophysical properties and functional roles of proteins predicted to bind RNA G-quadruplexes.

Main Methods:

• Combined theoretical predictions and experimental approaches to identify RNA G-quadruplex-binding proteins.
• Integrated experimental data with computational methods to create a prediction tool for RNA G-quadruplex-binding probability.
• Analyzed biophysical properties (disorder, hydrophilicity) of predicted RNA G-quadruplex-binding proteins.

Main Results:

• Demonstrated that numerous chromatin-binding proteins bind to RNA G-quadruplexes.
• Developed a prediction tool (G4-FUNNIES) that assigns a probability score for nuclear protein binding to RNA G-quadruplexes.
• Found that predicted RNA G-quadruplex-binding proteins are often disordered and hydrophilic, suggesting roles in transcription and phase separation.

Conclusions:

• Many nuclear proteins, particularly those involved in chromatin, can bind RNA G-quadruplexes.
• The developed prediction tool offers insights into RNA G-quadruplex-protein interactions and their functional implications.
• RNA G-quadruplex interactions may be linked to transcriptional regulation and the formation of membrane-less organelles.