Liquid-liquid phase separation (LLPS) of RNA-protein complexes plays a major role in the cellular function of membraneless organelles (MLOs). MLOs are sensitive to changes in cellular conditions, such as fluctuations in cytoplasmic ion concentrations. To investigate the effect of these changes on MLOs, we studied the influence of divalent cations on the physical and chemical properties of RNA coacervates. Using a model system comprised of an arginine-rich peptide and RNA, we predicted and observed that variations in signaling cations exert interaction-dependent effects on RNA LLPS. Changing the ionic environment has opposing effects on the propensity for heterotypic peptide-RNA and homotypic RNA LLPS, which results in a switch between coacervate types. Furthermore, divalent ion variations continuously tune the microenvironments and fluid properties of heterotypic and homotypic droplets. Our results may provide a general mechanism for modulating the biochemical environment of RNA coacervates in a cellular context.
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http://dx.doi.org/10.1038/s41598-019-48457-x | DOI Listing |
Biomacromolecules
December 2024
School of Chemistry and the UNSW RNA Institute, UNSW Sydney, Sydney, NSW 2052, Australia.
Membraneless organelles, often referred to as condensates or coacervates, are liquid-liquid phase-separated systems formed between noncoding RNAs and intrinsically disordered proteins. While the importance of different amino acid residues in short peptide-based condensates has been investigated, the role of the individual nucleobases or the type of heterocyclic structures, the purine vs pyrimidine nucleobases, is less researched. The cell's crowded environment has been mimicked to demonstrate its ability to induce the formation of condensates, but more research in this area is required, especially with respect to RNA-facilitated phase separation and the properties of the crowding agent, poly(ethylene glycol) (PEG).
View Article and Find Full Text PDFJ Mater Chem B
January 2025
New Chemistry Unit and School of Advanced Materials (SAMat), Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore 560064, India.
Phase separation and phase transitions pervade the biological domain, where proteins and RNA engage in liquid-liquid phase separation (LLPS), forming liquid-like membraneless organelles. The misregulation or dysfunction of these proteins culminates in the formation of solid aggregates a liquid-to-solid transition, leading to pathogenic conditions. To decipher the underlying mechanisms, synthetic LLPS has been examined through complex coacervate formation from charged polymers.
View Article and Find Full Text PDFNucleic Acids Res
October 2024
School of Life Sciences, State Key Laboratory of Oncology in South China, Cancer Center, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, China.
Liquid-liquid phase separation (LLPS) is a crucial process for the formation of biomolecular condensates such as coacervate droplets, P-bodies and stress granules, which play critical roles in many physiological and pathological processes. Increasing studies have shown that not only proteins but also RNAs play a critical role in LLPS. To host LLPS-associated RNAs, we previously developed a database named 'RPS' in 2021.
View Article and Find Full Text PDFNucleic Acids Res
November 2024
Department of Cell Biology, Faculty of Science, Charles University, Viničná 7, Prague 12800, Czech Republic.
The ribosome, owing to its exceptional conservation, harbours a remarkable molecular fossil known as the protoribosome. It surrounds the peptidyl transferase center (PTC), responsible for peptide bond formation. While previous studies have demonstrated the PTC activity in RNA alone, our investigation reveals the intricate roles of the ribosomal protein fragments (rPeptides) within the ribosomal core.
View Article and Find Full Text PDFSci Adv
August 2024
Howard Hughes Medical Institute, Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
Membraneless coacervate microdroplets have long been proposed as model protocells as they can grow, divide, and concentrate RNA by natural partitioning. However, the rapid exchange of RNA between these compartments, along with their rapid fusion, both within minutes, means that individual droplets would be unable to maintain their separate genetic identities. Hence, Darwinian evolution would not be possible, and the population would be vulnerable to collapse due to the rapid spread of parasitic RNAs.
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