Version 1
: Received: 1 May 2024 / Approved: 2 May 2024 / Online: 2 May 2024 (08:03:33 CEST)
How to cite:
Chen, H.; Li, B.; Zhao, X.; Yang, C.; Zhou, S.; Ma, W. Cell-Free Analysis Reveals the Role of RG/RGG Motifs in DDX3X Phase Separation and Their Potential Link to Cancer Pathogenesis. Preprints2024, 2024050106. https://doi.org/10.20944/preprints202405.0106.v1
Chen, H.; Li, B.; Zhao, X.; Yang, C.; Zhou, S.; Ma, W. Cell-Free Analysis Reveals the Role of RG/RGG Motifs in DDX3X Phase Separation and Their Potential Link to Cancer Pathogenesis. Preprints 2024, 2024050106. https://doi.org/10.20944/preprints202405.0106.v1
Chen, H.; Li, B.; Zhao, X.; Yang, C.; Zhou, S.; Ma, W. Cell-Free Analysis Reveals the Role of RG/RGG Motifs in DDX3X Phase Separation and Their Potential Link to Cancer Pathogenesis. Preprints2024, 2024050106. https://doi.org/10.20944/preprints202405.0106.v1
APA Style
Chen, H., Li, B., Zhao, X., Yang, C., Zhou, S., & Ma, W. (2024). Cell-Free Analysis Reveals the Role of RG/RGG Motifs in DDX3X Phase Separation and Their Potential Link to Cancer Pathogenesis. Preprints. https://doi.org/10.20944/preprints202405.0106.v1
Chicago/Turabian Style
Chen, H., Sa Zhou and Wenjian Ma. 2024 "Cell-Free Analysis Reveals the Role of RG/RGG Motifs in DDX3X Phase Separation and Their Potential Link to Cancer Pathogenesis" Preprints. https://doi.org/10.20944/preprints202405.0106.v1
Abstract
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. Bioinformatic analysis of cancer genomic datasets uncovered a significant enrichment of DDX3X mutations in RG/RGG motifs across multiple cancer types, particularly in the N-terminal region of the protein. 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.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
