2026-05-21 理化学研究所,バイオ産業情報化コンソーシアム,東京大学
DDX3XがmRNAを選択的に認識し、翻訳制御を行う分子機構の模式図
＜関連情報＞
DEADボックスRNAヘリカーゼDDX3XのN末端内在性無秩序領域における動的相互作用によって駆動される相分離 Phase Separation Driven by Dynamic Interactions in the N-Terminal Intrinsically Disordered Region of the DEAD-Box RNA Helicase DDX3X
Yuki Toyama,Shinichiro Inakami,Masaharu Takarada,Kohki Okabe,Koh Takeuchi,and Ichio Shimada
Journal of the American Chemical Society Published:May 20, 2026
DOI:https://doi.org/10.1021/jacs.5c22149
Abstract
The formation of membraneless organelles via liquid–liquid phase separation (LLPS) of proteins and RNAs has emerged as a central mechanism of cellular compartmentalization to finely regulate biological processes. DDX3X, a member of the DEAD-box RNA helicase family, is one of the global regulators of RNA-containing phase-separated organelles. While the importance of DDX3X in organelle formation is well-recognized, the molecular mechanisms underlying its RNA-driven LLPS remain poorly understood. In this study, we focused on the dynamic interactions between the N-terminal intrinsically disordered region (N-IDR) of DDX3X and G-quadruplex (GQ) RNA, which is a key regulator of physiological membraneless organelle assembly owing to its unique ability to promote LLPS. Using solution nuclear magnetic resonance spectroscopy, we identified hotspot regions for self-assembly within the N-IDR. These regions comprise charged stretches interspersed with key aromatic residues, whose interactions drive LLPS through a combination of electrostatic and π-interactions. Binding of GQ RNA effectively strengthens intermolecular interactions involving the arginine-rich segments of the N-IDR, providing molecular insights into its RNA-driven LLPS. We further discuss the functional implications of GQ-specific granule formation under stress conditions, highlighting the potential roles of DDX3X-GQ RNA interplay in cellular translational regulation.
