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

Johanna Luige, Alexandros Armaos, Gian Gaetano Tartaglia () and Ulf Andersson Vang Ørom ()
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Johanna Luige: Aarhus University
Alexandros Armaos: Istituto Italiano di Tecnologia (IIT)
Gian Gaetano Tartaglia: Istituto Italiano di Tecnologia (IIT)
Ulf Andersson Vang Ørom: Aarhus University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract RNA-binding proteins are central for many biological processes and their characterization has demonstrated a broad range of functions as well as a wide spectrum of target structures. RNA G-quadruplexes are important regulatory elements occurring in both coding and non-coding transcripts, yet our knowledge of their structure-based interactions is at present limited. Here, using theoretical predictions and experimental approaches, we show that many chromatin-binding proteins bind to RNA G-quadruplexes, and we classify them based on their RNA G-quadruplex-binding potential. Combining experimental identification of nuclear RNA G-quadruplex-binding proteins with computational approaches, we build a prediction tool that assigns probability score for a nuclear protein to bind RNA G-quadruplexes. We show that predicted G-quadruplex RNA-binding proteins exhibit a high degree of protein disorder and hydrophilicity and suggest involvement in both transcription and phase-separation into membrane-less organelles. Finally, we present the G4-Folded/UNfolded Nuclear Interaction Explorer System (G4-FUNNIES) for estimating RNA G4-binding propensities at http://service.tartaglialab.com/new_submission/G4FUNNIES .

Date: 2024
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DOI: 10.1038/s41467-024-46731-9

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