Biomolecular condensates in cell biology and virology: Phase-separated membraneless organelles (MLOs)

• Published in: Analytical biochemistry 2020-05, Vol.597, p.113691-113691, Article 113691
• Main Authors: Sehgal, Pravin B., Westley, Jenna, Lerea, Kenneth M., DiSenso-Browne, Susan, Etlinger, Joseph D.
• Format: Article
• Language: English
• Subjects: 2D and 3D supramolecular assemblies; Biomolecular condensates; Cell Biology; Cell Nucleus - chemistry; Cell Nucleus - virology; Cytoplasm - chemistry; Cytoplasm - virology; Cytoplasmic crowding; Humans; Liquid-like phase separation (LLPS); Membraneless organelles (MLOs); Myxovirus Resistance Proteins - chemistry; Myxovirus Resistance Proteins - isolation & purification; Myxovirus-resistance proteins MxA and Mx1; Neurodegenerative diseases; Organelles - chemistry; Organelles - virology
• ISSN: 0003-2697; 1096-0309
• DOI: 10.1016/j.ab.2020.113691

Membraneless organelles (MLOs) in the cytoplasm and nucleus in the form of 2D and 3D phase-separated biomolecular condensates are increasingly viewed as critical in regulating diverse cellular functions. These functions include cell signaling, immune synapse function, nuclear transcription, RNA splicing and processing, mRNA storage and translation, virus replication and maturation, antiviral mechanisms, DNA sensing, synaptic transmission, protein turnover and mitosis. Components comprising MLOs often associate with low affinity; thus cell integrity can be critical to the maintenance of the full complement of respective MLO components. Phase-separated condensates are typically metastable (shape-changing) and can undergo dramatic, rapid and reversible assembly and disassembly in response to cell signaling events, cell stress, during mitosis, and after changes in cytoplasmic “crowding” (as observed with condensates of the human myxovirus resistance protein MxA). Increasing evidence suggests that neuron-specific aberrations in phase-separation properties of RNA-binding proteins (e.g. FUS and TDP-43) and others (such as the microtubule-binding protein tau) contribute to the development of degenerative neurological diseases (e.g. amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer's disease). Thus, studies of liquid-like phase separation (LLPS) and the formation, structure and function of MLOs are of considerable importance in understanding basic cell biology and the pathogenesis of human diseases. •Liquid-like phase separation (LLPS) forms 2D and 3D phase-separated “biomolecular condensates”.•These comprise membraneless organelles (MLOs) which can serve diverse cellular functions.•Neuron-specific aberrations in condensates contribute to pathophysiology of neurological diseases.•Studies of MLOs and their regulated phase transitions help understand basic cell biology and disease pathogenesis.