Journal
BIOSCIENCE TRENDS
Volume 16, Issue 6, Pages 389-404Publisher
IRCA-BSSA
DOI: 10.5582/bst.2022.01449
Keywords
Biomacromolecule; phase transition; membrane-less organelles (MLOs); human diseases; therapeutic targets
Categories
Funding
- Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Natural Science Foundation of Shaanxi Province
- Key R&D Projects in Shaanxi Province
- Fundamental Research Funds for the Central Universities
- [82072106]
- [32101055]
- [2020 M683573]
- [2021JQ-128]
- [2021SF-242]
- [D5000210746]
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RNA-binding proteins play a central role in post-transcriptional regulation and protein synthesis. They also participate in the formation of membrane-less organelles through liquid-liquid phase separation. Understanding the potential roles and mechanisms of RNA-binding proteins in driving liquid-liquid phase separation is crucial for understanding cellular physiology and pathology.
RNA-binding proteins (RBPs) lie at the center of post-transcriptional regulation and protein synthesis, adding complexity to RNA life cycle. RBPs also participate in the formation of membrane-less organelles (MLOs) via undergoing liquid-liquid phase separation (LLPS), which underlies the formation of MLOs in eukaryotic cells. RBPs-triggered LLPS mainly relies on the interaction between their RNA recognition motifs (RRMs) and capped mRNA transcripts and the heterotypic multivalent interactions between their intrinsically disordered regions (IDRs) or prion-like domains (PLDs). In turn, the aggregations of RBPs are also dependent on the process of LLPS. RBPs-driven LLPS is involved in many intracellular processes (regulation of translation, mRNA storage and stabilization and cell signaling) and serves as the heart of cellular physiology and pathology. Thus, it is essential to comprehend the potential roles and investigate the internal mechanism of RPBs-triggered LLPS. In this review, we primarily expound on our current understanding of RBPs and they-triggered LLPS and summarize their physiological and pathological functions. Furthermore, we also summarize the potential roles of RBPs-triggered LLPS as novel therapeutic mechanism for human diseases. This review will help understand the mechanisms underlying LLPS and downstream regulation of RBPs and provide insights into the pathogenesis and therapy of complex diseases.
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