Let’s phase it: viruses are master architects of biomolecular condensates

Sagan, Selena M.; Weber, Stephanie C.

doi:10.1016/j.tibs.2022.09.008

Cited by 39 publications

(27 citation statements)

References 98 publications

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“…The advantage for the cell becomes immediately apparent, as a slight change in the protein’s local concentration can induce compartment formation or dissolution. Many cellular processes depend on LLPS, such as transcription, RNA processing, DNA damage response, or intracellular signaling (reviewed in [ 3 , 13 , 14 ]).…”

Section: What Is the Function Of Llps In Cell Biology?mentioning

confidence: 99%

“…This was first shown to be the case for Negri bodies, the characteristic inclusion bodies of rabies virus-infected cells [ 15 ]. Since then, several RNA viruses such as vesicular stomatitis virus, measles virus, rotavirus, influenza virus, and SARS coronavirus have been shown to form phase-separated compartments [ 16 – 22 ], and others are suspected to do the same (reviewed in [ 2 , 3 ]). PS is usually driven by the viral RNA-binding nucleoprotein, alone or in combination with other viral proteins.…”

Section: Do Viruses Make Use Of Llps and What For?mentioning

confidence: 99%

“…Here, we outline the basic principles of their formation and how viruses generate such compartments for replication and morphogenesis. As excellent in-depth reviews have recently been published [ 1 – 3 ], this article is meant to serve as a brief introduction to the field.…”

Section: Introductionmentioning

confidence: 99%

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Viral dew: Phase separation and the formation of viral replication compartments

Bosse

Brune

2023

PLoS Pathog

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Section: What Is the Function Of Llps In Cell Biology?mentioning

confidence: 99%

Section: Do Viruses Make Use Of Llps and What For?mentioning

confidence: 99%

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Viral dew: Phase separation and the formation of viral replication compartments

Bosse

Brune

2023

PLoS Pathog

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“…Also, P6 condensates in transgenic plants, as well as during early infections are spherical, but become distorted during disease progression and fusion of smaller condensates to the large amorphous VFs, which is consistent with the immobility of P6 within these foci. The importance of phase-separation and condensation during virus infection is becoming more and more evident in animal virus systems (Sagan & Weber, 2022) and the CaMV VFs provide a powerful model to study these processes during plant virus infections.…”

Section: The Camv Viral Factory -A Viral Rna Granule?mentioning

confidence: 99%

Stress & Granules : regulation of Cauliflower mosaic virus disease in Arabidopsis thaliana

Hoffmann¹

2023

Acta Universitatis Agriculturae Sueciae

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Viruses exist in intimate relationships with the organisms they are infecting and are just as dependent on compatibility with their host’s cellular components as they are on subverting them. During any virus infection, the cells are flooded with foreign nucleic acids (DNA and/or RNA) and have learned to recognize, disarm, or eliminate them. In turn, viruses have evolved to use the cellular transcription and RNA regulatory machinery for their own benefit. Cytoplasmic RNA granules, namely Processing bodies (PBs) and Stress granules (SGs) are at the forefront of RNA regulation as they contain and store untranslated RNA and are responsive in number, size, and composition to various stresses, including virus infection. For this thesis, we have explored the role of Arabidopsis thaliana RNA granules during infection with the pararetrovirus Cauliflower mosaic virus (CaMV). We show that PB components aid virus accumulation through shielding of the viral RNA from the antiviral RNA silencing machinery (Paper I). In addition, we find that the cytoplasmic viral replication factory contains several RNA granule proteins during infection, including both, PB components and SG components. Opposite to PBs, SGs are likely antiviral and CaMV subverts their biogenesis through its multifunctional protein P6 (Paper II). In an effort to uncover novel disease determinants, we explore the variation of CaMV disease in naturally occurring populations of Arabidopsis thaliana and uncover the importance of the plant hormone abscisic acid and its homeostasis for CaMV infection, as well as a novel CaMV susceptibility factor, the ABA synthesis gene NCED9 (Paper III).

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“…These membraneless organelles (MLOs) are responsible for strategic cellular organization in response to changing environments including endogenous and exogenous stress [ 14 , 19 , 20 , 21 ]. MLOs are ubiquitously utilized not only by all eukaryotes, but also bacteria [ 22 ], and viruses which are now recognized as master architects of biomolecular condensates, using phase separation to form viral replication “factories” [ 23 , 24 ]. The disruption of phase separation in key cellular processes results in diseases including neurodegenerative disorders and cancer [ 25 , 26 , 27 , 28 , 29 ].…”

Section: Aberrant Phase Separation Is the Fundamental Molecular Drive...mentioning

confidence: 99%

Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia

Loh¹,

Reíter

2023

IJMS

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The swift rise in acceptance of molecular principles defining phase separation by a broad array of scientific disciplines is shadowed by increasing discoveries linking phase separation to pathological aggregations associated with numerous neurodegenerative disorders, including Alzheimer’s disease, that contribute to dementia. Phase separation is powered by multivalent macromolecular interactions. Importantly, the release of water molecules from protein hydration shells into bulk creates entropic gains that promote phase separation and the subsequent generation of insoluble cytotoxic aggregates that drive healthy brain cells into diseased states. Higher viscosity in interfacial waters and limited hydration in interiors of biomolecular condensates facilitate phase separation. Light, water, and melatonin constitute an ancient synergy that ensures adequate protein hydration to prevent aberrant phase separation. The 670 nm visible red wavelength found in sunlight and employed in photobiomodulation reduces interfacial and mitochondrial matrix viscosity to enhance ATP production via increasing ATP synthase motor efficiency. Melatonin is a potent antioxidant that lowers viscosity to increase ATP by scavenging excess reactive oxygen species and free radicals. Reduced viscosity by light and melatonin elevates the availability of free water molecules that allow melatonin to adopt favorable conformations that enhance intrinsic features, including binding interactions with adenosine that reinforces the adenosine moiety effect of ATP responsible for preventing water removal that causes hydrophobic collapse and aggregation in phase separation. Precise recalibration of interspecies melatonin dosages that account for differences in metabolic rates and bioavailability will ensure the efficacious reinstatement of the once-powerful ancient synergy between light, water, and melatonin in a modern world.

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Let’s phase it: viruses are master architects of biomolecular condensates

Cited by 39 publications

References 98 publications

Viral dew: Phase separation and the formation of viral replication compartments

Viral dew: Phase separation and the formation of viral replication compartments

Stress & Granules : regulation of Cauliflower mosaic virus disease in Arabidopsis thaliana

Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia

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