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Biomolecular condensates: organizers of cellular biochemistry

TLDR
This work has shown that liquid–liquid phase separation driven by multivalent macromolecular interactions is an important organizing principle for biomolecular condensates and has proposed a physical framework for this organizing principle.
Abstract
In addition to membrane-bound organelles, eukaryotic cells feature various membraneless compartments, including the centrosome, the nucleolus and various granules. Many of these compartments form through liquid–liquid phase separation, and the principles, mechanisms and regulation of their assembly as well as their cellular functions are now beginning to emerge. Biomolecular condensates are micron-scale compartments in eukaryotic cells that lack surrounding membranes but function to concentrate proteins and nucleic acids. These condensates are involved in diverse processes, including RNA metabolism, ribosome biogenesis, the DNA damage response and signal transduction. Recent studies have shown that liquid–liquid phase separation driven by multivalent macromolecular interactions is an important organizing principle for biomolecular condensates. With this physical framework, it is now possible to explain how the assembly, composition, physical properties and biochemical and cellular functions of these important structures are regulated.

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Citations
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Journal ArticleDOI

Liquid phase condensation in cell physiology and disease.

TL;DR: The findings together suggest that several membrane-less organelles have been shown to exhibit a concentration threshold for assembly, a hallmark of phase separation, and represent liquid-phase condensates, which form via a biologically regulated (liquid-liquid) phase separation process.
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Gene regulation by long non-coding RNAs and its biological functions.

TL;DR: A review of the mechanisms of lncRNA biogenesis, localization and functions in transcriptional, post-transcriptional and other modes of gene regulation, and their potential therapeutic applications is presented in this article.
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Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates.

TL;DR: In this article, the authors propose guidelines for rigorous experimental characterization of liquid-liquid phase separation processes in vitro and in cells, discuss the caveats of common experimental approaches, and point out experimental and theoretical gaps in the field.
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Regulation of microRNA function in animals

TL;DR: The mechanisms that modulate miRNA activity, stability and cellular localization through alternative processing and maturation, sequence editing, post-translational modifications of Argonaute proteins, subcellular localization and regulation of miRNA–target interactions are reviewed.
References
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Journal ArticleDOI

Thermodynamics of High Polymer Solutions

TL;DR: In this paper, a statistical treatment of high polymer solutions has been carried out on the basis of an idealized model, originally proposed by Meyer, which is analogous to the one ordinarily assumed in the derivation of the ''ideal'' solution laws for molecules of equal size.
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Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation

TL;DR: It is shown that P granules exhibit liquid-like behaviors, including fusion, dripping, and wetting, which is used to estimate their viscosity and surface tension, and reflects a classic phase transition, in which polarity proteins vary the condensation point across the cell.
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Liquid-liquid phase separation in biology.

TL;DR: The basic physical concepts necessary to understand the consequences of liquid-like states for biological functions are discussed.
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A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation

TL;DR: It is proposed that liquid-like compartments carry the trade-off between functionality and risk of aggregation and that aberrant phase transitions within liquid- like compartments lie at the heart of ALS and, presumably, other age-related diseases.
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