Biomolecular condensates (BMCs) represent a group of organized and programmed systems that participate in gene transcription, chromosome organization, cell division, tumorigenesis, and aging. However, the understanding of BMCs in terms of internal organizations and external regulations remains at an early stage. Recently, novel approaches such as synthetic biology have been used for de novo synthesis of BMCs. These synthesized BMCs (SBMCs) driven by phase separation adeptly resemble the self-assembly and dynamics of natural biomolecular condensates, offering vast potentials in basic and applied research. This review introduces recent progresses in phase separation-induced SBMCs, attempting to elaborate on the intrinsic principles and regulatory methodologies used to construct SBMCs. Furthermore, the scientific applications of SBMCs are illustrated, as indicated by the studies of chromosome structure, pathogenesis, bio-manufacturing, artificial cell design, and drug delivery. The controllable SBMCs offer a powerful tool for understanding metabolic regulations, cellular organizations, and disease-associated protein aggregations, raising both opportunities and challenges in the future of biomaterial, biotechnology, and biomedicine.
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http://dx.doi.org/10.1016/j.jbc.2025.108188 | DOI Listing |
J Biol Chem
January 2025
CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China. Electronic address:
Biomolecular condensates (BMCs) represent a group of organized and programmed systems that participate in gene transcription, chromosome organization, cell division, tumorigenesis, and aging. However, the understanding of BMCs in terms of internal organizations and external regulations remains at an early stage. Recently, novel approaches such as synthetic biology have been used for de novo synthesis of BMCs.
View Article and Find Full Text PDFCurr Opin Genet Dev
January 2025
MCD, Center for Integrative Biology (CBI), University of Toulouse, CNRS, Toulouse, France. Electronic address:
Membraneless subcompartments organize various activities in the cell nucleus. Some of them are formed through phase separation that is driven by the polymeric and multivalent nature of biomolecules. Here, we discuss the role of RNAs in regulating nuclear subcompartments.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
Biomolecular condensation lays the foundation of forming biologically important membraneless organelles, but abnormal condensation processes are often associated with human diseases. Ribonucleic acid (RNA) plays a critical role in the formation of biomolecular condensates by mediating the phase transition through its interactions with proteins and other RNAs. However, the physicochemical principles governing RNA phase transitions, especially for short RNAs, remain inadequately understood.
View Article and Find Full Text PDFPLoS Comput Biol
January 2025
Department of Physical-Chemistry, Complutense University of Madrid, Madrid, Spain.
Intracellular liquid-liquid phase separation (LLPS) of proteins and nucleic acids is a fundamental mechanism by which cells compartmentalize their components and perform essential biological functions. Molecular simulations play a crucial role in providing microscopic insights into the physicochemical processes driving this phenomenon. In this study, we systematically compare six state-of-the-art sequence-dependent residue-resolution models to evaluate their performance in reproducing the phase behaviour and material properties of condensates formed by seven variants of the low-complexity domain (LCD) of the hnRNPA1 protein (A1-LCD)-a protein implicated in the pathological liquid-to-solid transition of stress granules.
View Article and Find Full Text PDFCurr Biol
January 2025
Department of Developmental Biology and Cancer Research, The Hebrew University of Jerusalem Faculty of Medicine, Ein-Kerem Campus, Jerusalem 9112102, Israel; Institute for Medical Research, Israel-Canada (IMRIC), Ein-Kerem Campus, Jerusalem 9112102, Israel. Electronic address:
Vertebrate oocyte polarity has been observed for two centuries and is essential for embryonic axis formation and germline specification, yet its underlying mechanisms remain unknown. In oocyte polarization, critical RNA-protein (RNP) granules delivered to the oocyte's vegetal pole are stored by the Balbiani body (Bb), a membraneless organelle conserved across species from insects to humans. However, the mechanisms of Bb formation are still unclear.
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