D-aring to explore: New approaches to gasdermin D targeting DOI
Lei Wang, Wen Zhou

Cell chemical biology, Journal Year: 2024, Volume and Issue: 31(12), P. 2015 - 2017

Published: Dec. 1, 2024

Language: Английский

Nanoplastic-Induced Antibody Liquid-liquid Phase Separation: Insights into Potential Immunotoxic Implications DOI
Mei Dang, Longjiang Wu, Hongwei Bai

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 487, P. 137170 - 137170

Published: Jan. 9, 2025

Language: Английский

Citations

0
cGAS-STING: mechanisms and therapeutic opportunities DOI
Mengyuan Zhang, Changxin Wu, Defen Lu

et al.

Science China Life Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Language: Английский

Citations

0
R-loops in neurodegeneration DOI Creative Commons
Chiara Beghè,

Helena Harpham,

Yasmine Barberic

et al.

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102345 - 102345

Published: April 8, 2025

Neurodegenerative diseases are associated with the progressive loss of neurons. R-loops non-canonical nucleic acid structures formed during transcription and composed an RNA/DNA hybrid a displaced single-stranded DNA. Whilst important regulators cellular processes, they also pathologies multiple disorders, including repeat expansion, motor neuron, inflammatory ageing diseases. In this review, we discuss how contribute to pathological mechanisms that underpin neurodegeneration. We highlight role in several hallmarks neurodegenerative RNA DNA defects, damage, protein aggregation, inflammation, mitochondrial dysfunction, neuronal cell death. potential as therapeutic targets for disorders.

Language: Английский

Citations

0
YTHDC1 phase separation drives the nuclear export of m6A-modified lncNONMMUT062668.2 through the transport complex SRSF3–ALYREF–XPO5 to aggravate pulmonary fibrosis DOI Creative Commons
Sony Su Chen,

Yujie Wang,

Jinjin Zhang

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 12, 2025

Fibroblast-to-myofibroblast differentiation is the main cytopathologic characteristic of pulmonary fibrosis. However, its underlying molecular mechanism remains poorly understood. This study elucidated that nuclear export lncNONMMUT062668.2 (lnc668) exacerbated fibrosis by activating fibroblast-to-myofibroblast differentiation. Mechanistic research revealed histone H3K9 lactylation in promoter region N6-methyladenosine (m6A) writer METTL3 was enriched to enhance transcription, leading lnc668 m6A modification. Meanwhile, reader YTHDC1 recognized m6A-modified and elevated METTL3-mediated Subsequently, phase-separating promoted lnc668. In this process, formed a pore complex with serine/arginine-rich splicing factor 3, Aly/REF factor, exportin-5 assist translocation from nucleus cytoplasm. After export, facilitated translation stability host gene phosphatidylinositol-binding clathrin assembly protein activate differentiation, aggravation fibrosis, which also depended on phase separation. first clarified separation crucial for modification, profibrotic role exacerbating These findings provide new insights into cytoplasmic lncRNAs identified potential targets therapy.

Language: Английский

Citations

0
Biomolecular condensates with liquid properties formed during viral infections DOI Creative Commons
Damien Glon,

Benjamin Léonardon,

Ariane Guillemot

et al.

Microbes and Infection, Journal Year: 2024, Volume and Issue: 26(8), P. 105402 - 105402

Published: Aug. 8, 2024

During a viral infection, several membraneless compartments with liquid properties are formed. They can be of origin concentrating proteins and nucleic acids, harboring essential stages the cycle, or cellular containing components involved in innate immunity. This is paradigm shift our understanding replication interaction between viruses

Language: Английский

Citations

3
Biomolecular condensates: phasing in regulated host–pathogen interactions DOI
Kun Chen, Xuetao Cao

Trends in Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

1
Dimerization-dependent gel-like condensation with dsDNA underpins the activation of human cGAS DOI

Jacob Lueck,

Alexander Strom, Shuai Wu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 8, 2024

Abstract Cyclic G/AMP Synthase (cGAS) initiates inflammatory responses against pathogenic double-stranded (ds)DNA. Although it is well established that cGAS forms phase-separated condensates with dsDNA, their function remains poorly defined. We report here the dimerization of on dsDNA creates a mesh-like network, leading to gel-like condensate formation. binds and various nucleic acids, only permits necessary for activation gelation. co-condenses other acids but retains distinct dsDNA-mediated substate, which single-stranded RNA can dissolve deactivate enzyme. Moreover, gel-like, not liquid-like, condensation protects bound from exonucleases, also limits mobility NTPs dinucleotide intermediate efficient cGAMP synthesis. Together, our results show enzymes finetune surrounding microenvironments regulate signaling activities.

Language: Английский

Citations

0
The emerging roles of liquid–liquid phase separation in tumor immunity DOI
Yuan‐Tong Liu,

Lin-Yu Cao,

Zhi‐Jun Sun

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113212 - 113212

Published: Sept. 30, 2024

Language: Английский

Citations

0
Protein-RNA condensation kinetics via filamentous nanoclusters DOI Creative Commons

Ramón Peralta Martínez,

Araceli Visentín, Mariano Salgueiro

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Abstract Protein-RNA phase separation is at the center of membraneless biomolecular condensates governing cell physiology and pathology. Using an archetypical viral protein-RNA condensation model, we determined sequence events that starts with sub-second formation a protomer two RNAs per protein dimer. Association additional RNA molecules to weaker secondary binding sites in this kickstarts crystallization-like assembly molecular condensate. Primary nucleation faster than sum growth, which multistep process. nuclei grow over hundreds seconds into filaments subsequently nanoclusters circa 600 nm diameter. Cryoelectron microscopy reveals internal structure formed by incoming layers made ribonucleoprotein oligomers, reminiscent genome packing nucleocapsid. These progress liquid condensate droplets undergo further partial coalescence yield typical hydrogel-like coacervates may represent scaffold large factory infected cells. Our integrated experimental kinetic investigation exposes rate limiting steps structures along key biological pathway present across life kingdoms.

Language: Английский

Citations

0
Liquid-liquid separation in gut immunity DOI Creative Commons
Zhaoyang Wang, Lili Zhou, Xiaolan Zhong

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 10, 2024

Gut immunity is essential for maintaining intestinal health. Recent studies have identified that intracellular liquid-liquid phase separation (LLPS) may play a significant role in regulating gut immunity, however, the underlying mechanisms remain unclear. LLPS refers to droplet condensates formed through molecular interactions, which are crucial formation of membraneless organelles and biomolecules. can contribute tight junctions between epithelial cells influence colonization probiotics intestine, thereby protecting immune system by integrity barrier stability microbiota. Additionally, affect microclusters on plasma membrane T cells, resulting increased density reduced mobility, turn influences cell functionality. The occurrence intricately associated with initiation progression immunity. This review introduces mechanism analyzes future research directions potential applications this phenomenon.

Language: Английский

Citations

0