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Liquid-liquid phase separation of DDX3X: mechanisms, pathological implications, and therapeutic potential
Minxiang Zhong1, Shiyuan Chen1, Wengqi Lu1
1School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, Jiangsu, China.
Abstract:
DDX3X is a multifunctional DEAD-box RNA helicase that plays pivotal roles in diverse biological processes, including RNA metabolism, translation regulation, and the progression of various diseases such as intellectual disabilities, inflammation, viral infections, and cancer. Over the past decades, extensive research has unveiled the physiological and pathological functions of DDX3X. However, the precise molecular mechanisms underlying these processes remain incompletely understood, limiting the development of targeted therapies for DDX3X-related diseases. Recent studies have revealed that DDX3X can undergo liquid-liquid phase separation (LLPS), a biophysical phenomenon driven by multivalent weak interactions, which has been implicated in a wide range of physiological and pathological contexts. Understanding how LLPS contributes to DDX3X's multifaceted functions has emerged as a critical area of investigation. In this review, we provide a comprehensive overview of the molecular mechanisms governing DDX3X LLPS and its biological implications. We also discuss the functional consequences of DDX3X mutations that disrupt proper LLPS and examine the sexually dimorphic LLPS properties between DDX3X and its Y-chromosome homolog, DDX3Y. Finally, we highlight potential therapeutic strategies targeting LLPS as a novel approach for treating DDX3X-related diseases.
Insights
DDX3X, a key RNA helicase, forms liquid-like droplets (LLPS) influencing cell processes and diseases. Understanding DDX3X LLPS mechanisms offers new therapeutic targets for conditions like cancer and intellectual disabilities.
Area of Science:
- Molecular Biology
- Biophysics
- Genetics
Background:
- DDX3X is a crucial DEAD-box RNA helicase involved in RNA metabolism, translation, and disease.
- Its precise molecular mechanisms, particularly in disease pathogenesis, are not fully understood.
- Liquid-liquid phase separation (LLPS) is increasingly recognized as a key regulatory mechanism in cellular processes.
Purpose of the Study:
- To provide a comprehensive overview of DDX3X liquid-liquid phase separation (LLPS).
- To elucidate the molecular mechanisms governing DDX3X LLPS and its biological implications.
- To explore therapeutic strategies targeting DDX3X LLPS for disease treatment.
Main Methods:
- Literature review of studies on DDX3X function, LLPS, and related diseases.
- Analysis of molecular mechanisms underlying DDX3X LLPS.
- Examination of DDX3X mutations affecting LLPS and comparison with DDX3Y.
Main Results:
- DDX3X undergoes LLPS, a phenomenon implicated in various physiological and pathological contexts.
- Mutations in DDX3X can disrupt its LLPS, leading to functional consequences.
- Sexually dimorphic LLPS properties exist between DDX3X and its Y-chromosome homolog, DDX3Y.
Conclusions:
- Understanding DDX3X LLPS is critical for deciphering its multifaceted roles in health and disease.
- Targeting DDX3X LLPS presents a promising novel therapeutic avenue for DDX3X-related disorders.
- Further research into DDX3X LLPS mechanisms and therapeutic potential is warranted.
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