Liquid-Liquid Phase Separation

Topic Information

Dear Colleagues,

Liquid-liquid phase separation (LLPS) underlies the formation of membraneless organelles and is a critical component of cellular organization. These dynamic organelles selectively recruit molecules and exhibit similar physical properties (liquid-like behaviour, capacity to undergo phase transitions) in response to external stimuli (temperature, osmotic potential etc), or their chemical composition (posttranslational modifications, RNA, etc). Such dynamic nature allows them to rapidly assemble or dissemble to accommodate various cellular changes, as well as adopt more structural roles, such as nucleation of microtubules by centrosomes, or ribosomal assembly taking place in nucleoli. The material properties of liquid organelles are likely to reflect their functions, and it has been shown that aberrant phase transitions are implicated in multiple pathologies, including neurodegeneration and cancer development. Recent studies have also revealed multiple examples of LLPS involved in viral infections, where phase separation play roles in replication of SARS-CoV-2, HIV, rotaviruses or influenza A virus, all of which seem to utilize liquid organelles to compartmentalize viral replication machinery. The aim of our Special Topic is to address recent advances in this field to provide perspectives in this emerging area of research. It also aims at exploring open questions about the fundamental physico-chemical principles of the LLPS phenomena in order to study them in the context of cellular functions and human diseases.

Dr. Maria João Amorim
Dr. Yohei Yamauchi
Dr. Alexander Borodavka
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
COVID covid	-	-	2021	17.7 Days	CHF 1000
International Journal of Molecular Sciences ijms	4.9	8.1	2000	18.1 Days	CHF 2900
Microorganisms microorganisms	4.1	7.4	2013	13.4 Days	CHF 2700
Viruses viruses	3.8	7.3	2009	16.1 Days	CHF 2600

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Published Papers (5 papers)

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All COVID IJMS Microorganisms Viruses

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10 pages, 513 KiB  

Open AccessCommentary

Herpesvirus Replication Compartments: Dynamic Biomolecular Condensates?

by Enrico Caragliano, Wolfram Brune and Jens B. Bosse

Viruses 2022, 14(5), 960; https://doi.org/10.3390/v14050960 - 4 May 2022

Cited by 12 | Viewed by 3266

Abstract

Recent progress has provided clear evidence that many RNA-viruses form cytoplasmic biomolecular condensates mediated by liquid–liquid phase separation to facilitate their replication. In contrast, seemingly contradictory data exist for herpesviruses, which replicate their DNA genomes in nuclear membrane-less replication compartments (RCs). Here, we [...] Read more.

Recent progress has provided clear evidence that many RNA-viruses form cytoplasmic biomolecular condensates mediated by liquid–liquid phase separation to facilitate their replication. In contrast, seemingly contradictory data exist for herpesviruses, which replicate their DNA genomes in nuclear membrane-less replication compartments (RCs). Here, we review the current literature and comment on nuclear condensate formation by herpesviruses, specifically with regard to RC formation. Based on data obtained with human cytomegalovirus (human herpesvirus 5), we propose that liquid and homogenous early RCs convert into more heterogeneous RCs with complex properties over the course of infection. We highlight how the advent of DNA replication leads to the maturation of these biomolecular condensates, likely by adding an additional DNA scaffold. Full article

(This article belongs to the Topic Liquid-Liquid Phase Separation)

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21 pages, 3626 KiB  

Open AccessArticle

Nst1, Densely Associated to P-Body in the Post-Exponential Phases of Saccharomyces cerevisiae, Shows an Intrinsic Potential of Producing Liquid-Like Condensates of P-Body Components in Cells

by Yoon-Jeong Choi and Kiwon Song

Int. J. Mol. Sci. 2022, 23(5), 2501; https://doi.org/10.3390/ijms23052501 - 24 Feb 2022

Cited by 2 | Viewed by 2345

Abstract

Membrane-less biomolecular compartmentalization is a core phenomenon involved in many physiological activities that occur ubiquitously in cells. Condensates, such as promyelocytic leukemia (PML) bodies, stress granules, and P-bodies (PBs), have been investigated to understand the process of membrane-less cellular compartmentalization. In budding yeast, [...] Read more.

Membrane-less biomolecular compartmentalization is a core phenomenon involved in many physiological activities that occur ubiquitously in cells. Condensates, such as promyelocytic leukemia (PML) bodies, stress granules, and P-bodies (PBs), have been investigated to understand the process of membrane-less cellular compartmentalization. In budding yeast, PBs dispersed in the cytoplasm of exponentially growing cells rapidly accumulate in response to various stresses such as osmotic stress, glucose deficiency, and heat stress. In addition, cells start to accumulate PBs chronically in post-exponential phases. Specific protein–protein interactions are involved in accelerating PB accumulation in each circumstance, and discovering the regulatory mechanism for each is the key to understanding cellular condensation. Here, we demonstrate that Nst1 of budding yeast Saccharomyces cerevisiae is far more densely associated with PBs in post-exponentially growing phases from the diauxic shift to the stationary phase than during glucose deprivation of exponentially growing cells, while the PB marker Dcp2 exhibits a similar degree of condensation under these conditions. Similar to Edc3, ectopic Nst1 overexpression induces self-condensation and the condensation of other PB components, such as Dcp2 and Dhh1, which exhibit liquid-like properties. Altogether, these results suggest that Nst1 has the intrinsic potential for self-condensation and the condensation of other PB components, specifically in post-exponential phases. Full article

(This article belongs to the Topic Liquid-Liquid Phase Separation)

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20 pages, 3018 KiB  

Open AccessArticle

Evidence That the Adenovirus Single-Stranded DNA Binding Protein Mediates the Assembly of Biomolecular Condensates to Form Viral Replication Compartments

by Paloma Hidalgo, Arturo Pimentel, Diana Mojica-Santamaría, Konstantin von Stromberg, Helga Hofmann-Sieber, Christian Lona-Arrona, Thomas Dobner and Ramón A. González

Viruses 2021, 13(9), 1778; https://doi.org/10.3390/v13091778 - 6 Sep 2021

Cited by 19 | Viewed by 4788

Abstract

A common viral replication strategy is characterized by the assembly of intracellular compartments that concentrate factors needed for viral replication and simultaneously conceal the viral genome from host-defense mechanisms. Recently, various membrane-less virus-induced compartments and cellular organelles have been shown to represent biomolecular [...] Read more.

A common viral replication strategy is characterized by the assembly of intracellular compartments that concentrate factors needed for viral replication and simultaneously conceal the viral genome from host-defense mechanisms. Recently, various membrane-less virus-induced compartments and cellular organelles have been shown to represent biomolecular condensates (BMCs) that assemble through liquid-liquid phase separation (LLPS). In the present work, we analyze biophysical properties of intranuclear replication compartments (RCs) induced during human adenovirus (HAdV) infection. The viral ssDNA-binding protein (DBP) is a major component of RCs that contains intrinsically disordered and low complexity proline-rich regions, features shared with proteins that drive phase transitions. Using fluorescence recovery after photobleaching (FRAP) and time-lapse studies in living HAdV-infected cells, we show that DBP-positive RCs display properties of liquid BMCs, which can fuse and divide, and eventually form an intranuclear mesh with less fluid-like features. Moreover, the transient expression of DBP recapitulates the assembly and liquid-like properties of RCs in HAdV-infected cells. These results are of relevance as they indicate that DBP may be a scaffold protein for the assembly of HAdV-RCs and should contribute to future studies on the role of BMCs in virus-host cell interactions. Full article

(This article belongs to the Topic Liquid-Liquid Phase Separation)

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28 pages, 4173 KiB  

Open AccessReview

Liquid Biomolecular Condensates and Viral Lifecycles: Review and Perspectives

by Temitope Akhigbe Etibor, Yohei Yamauchi and Maria João Amorim

Viruses 2021, 13(3), 366; https://doi.org/10.3390/v13030366 - 25 Feb 2021

Cited by 70 | Viewed by 8036

Abstract

Viruses are highly dependent on the host they infect. Their dependence triggers processes of virus–host co-adaptation, enabling viruses to explore host resources whilst escaping immunity. Scientists have tackled viral–host interplay at differing levels of complexity—in individual hosts, organs, tissues and cells—and seminal studies [...] Read more.

Viruses are highly dependent on the host they infect. Their dependence triggers processes of virus–host co-adaptation, enabling viruses to explore host resources whilst escaping immunity. Scientists have tackled viral–host interplay at differing levels of complexity—in individual hosts, organs, tissues and cells—and seminal studies advanced our understanding about viral lifecycles, intra- or inter-species transmission, and means to control infections. Recently, it emerged as important to address the physical properties of the materials in biological systems; membrane-bound organelles are only one of many ways to separate molecules from the cellular milieu. By achieving a type of compartmentalization lacking membranes known as biomolecular condensates, biological systems developed alternative mechanisms of controlling reactions. The identification that many biological condensates display liquid properties led to the proposal that liquid–liquid phase separation (LLPS) drives their formation. The concept of LLPS is a paradigm shift in cellular structure and organization. There is an unprecedented momentum to revisit long-standing questions in virology and to explore novel antiviral strategies. In the first part of this review, we focus on the state-of-the-art about biomolecular condensates. In the second part, we capture what is known about RNA virus-phase biology and discuss future perspectives of this emerging field in virology. Full article

(This article belongs to the Topic Liquid-Liquid Phase Separation)

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14 pages, 1513 KiB  

Open AccessReview

Formation and Function of Liquid-Like Viral Factories in Negative-Sense Single-Stranded RNA Virus Infections

by Justin M. Su, Maxwell Z. Wilson, Charles E. Samuel and Dzwokai Ma

Viruses 2021, 13(1), 126; https://doi.org/10.3390/v13010126 - 18 Jan 2021

Cited by 33 | Viewed by 9860

Abstract

Liquid–liquid phase separation (LLPS) represents a major physiochemical principle to organize intracellular membrane-less structures. Studies with non-segmented negative-sense (NNS) RNA viruses have uncovered a key role of LLPS in the formation of viral inclusion bodies (IBs), sites of viral protein concentration in the [...] Read more.

Liquid–liquid phase separation (LLPS) represents a major physiochemical principle to organize intracellular membrane-less structures. Studies with non-segmented negative-sense (NNS) RNA viruses have uncovered a key role of LLPS in the formation of viral inclusion bodies (IBs), sites of viral protein concentration in the cytoplasm of infected cells. These studies further reveal the structural and functional complexity of viral IB factories and provide a foundation for their future research. Herein, we review the literature leading to the discovery of LLPS-driven formation of IBs in NNS RNA virus-infected cells and the identification of viral scaffold components involved, and then outline important questions and challenges for IB assembly and disassembly. We discuss the functional implications of LLPS in the life cycle of NNS RNA viruses and host responses to infection. Finally, we speculate on the potential mechanisms underlying IB maturation, a phenomenon relevant to many human diseases. Full article

(This article belongs to the Topic Liquid-Liquid Phase Separation)

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