Cell-free analysis reveals the role of RG/RGG motifs in DDX3X phase separation and their potential link to cancer pathogenesis.

Autor: Chen H; College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China., Li B; College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China., Zhao X; College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China., Yang C; College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China., Zhou S; College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China., Ma W; College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China; Qilu Institute of Technology, Shandong, China. Electronic address: ma_wj@tust.edu.cn.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Nov; Vol. 279 (Pt 2), pp. 135251. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1016/j.ijbiomac.2024.135251
Abstrakt: The DEAD-box RNA helicase DDX3X is a multifunctional protein involved in RNA metabolism and stress responses. In this study, we investigated the role of RG/RGG motifs in the dynamic process of liquid-liquid phase separation (LLPS) of DDX3X using cell-free assays and explored their potential link to cancer development through bioinformatic analysis. Our results demonstrate that the number, location, and composition of RG/RGG motifs significantly influence the ability of DDX3X to undergo phase separation and form self-aggregates. Mutational analysis revealed that the spacing between RG/RGG motifs and the number of glycine residues within each motif are critical factors in determining the extent of phase separation. Furthermore, we found that DDX3X is co-expressed with the stress granule protein G3BP1 in several cancer types and can undergo co-phase separation with G3BP1 in a cell-free system, suggesting a potential functional interaction between these proteins in phase-separated structures. DDX3X and G3BP1 may interact through their RG/RGG domains and subsequently exert important cellular functions under stress situation. Collectively, our findings provide novel insights into the role of RG/RGG motifs in modulating DDX3X phase separation and their potential contribution to cancer pathogenesis.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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