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Phase Separation Driven by Dynamic Interactions in the N-Terminal Intrinsically Disordered Region of the DEAD-Box RNA Helicase DDX3X - PubMed

4 hours ago
  • #RNA helicase
  • #intrinsically disordered region
  • #phase separation
  • Liquid-liquid phase separation (LLPS) is crucial for forming membraneless organelles in cells, with DDX3X, a DEAD-box RNA helicase, playing a key regulatory role in RNA-containing organelles.
  • The study investigates the molecular mechanisms of DDX3X's RNA-driven LLPS, focusing on interactions between its N-terminal intrinsically disordered region (N-IDR) and G-quadruplex (GQ) RNA, which promotes LLPS.
  • Using NMR spectroscopy, hotspot regions in the N-IDR were identified, involving charged stretches and aromatic residues that drive LLPS via electrostatic and π-interactions.
  • GQ RNA binding strengthens intermolecular interactions, particularly through arginine-rich segments of the N-IDR, offering insights into RNA-driven LLPS mechanisms.
  • The research highlights functional implications of GQ-specific granule formation under stress and the potential role of DDX3X-GQ RNA interplay in cellular translational regulation.