O-GlcNAcylation reduces proteome solubility and regulates the formation of biomolecular condensates in human cells DOI Creative Commons
Senhan Xu, Kejun Yin, Xing Xu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 30, 2025

O-GlcNAcylation plays critical roles in the regulation of protein functions and cellular activities, including interactions with other macromolecules. While formation biomolecular condensates (or biocondensates) regulated by a few individual proteins has been reported, systematic investigation on biocondensate remains to be explored. Here we systematically study regulating solubility its impacts RNA-protein using mass spectrometry-based chemoproteomics. Unexpectedly, observe system-wide decrease modified O-GlcNAcylation, glycoproteins involved focal adhesion actin binding exhibiting most significant decrease. Furthermore, sites located disordered regions fewer acidic aromatic residues nearby are related greater drop solubility. Additionally, discover that specific group events promotes dissociation under heat stress, while some enhance during recovery phase. Using site mutagenesis, inhibition O-GlcNAc transferase, fluorescence microscopy, validate regulates biocondensates for YTHDF3 NUFIP2. This work advances our understanding condensates.

Language: Английский

Stress-related biomolecular condensates in plants DOI Creative Commons
Jorge Solís-Miranda, Monika Chodasiewicz, Aleksandra Skirycz

et al.

The Plant Cell, Journal Year: 2023, Volume and Issue: 35(9), P. 3187 - 3204

Published: May 10, 2023

Biomolecular condensates are membraneless organelle-like structures that can concentrate molecules and often form through liquid-liquid phase separation. condensate assembly is tightly regulated by developmental environmental cues. Although research on biomolecular has intensified in the past 10 years, our current understanding of molecular mechanisms components underlying their formation remains its infancy, especially plants. However, recent studies have shown may be central to plant acclimation stress conditions. Here, we describe mechanism, regulation, properties stress-related plants, focusing granules processing bodies, 2 most well-characterized condensates. In this regard, showcase proteomes bodies an attempt suggest methods for elucidating composition function Finally, discuss how modulate responses they might used as targets biotechnological efforts improve tolerance.

Language: Английский

Citations

48
Identification of small molecule inhibitors of G3BP-driven stress granule formation DOI Creative Commons
Brian D. Freibaum, James Messing, Haruko Nakamura

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(3)

Published: Jan. 29, 2024

Stress granule formation is triggered by the release of mRNAs from polysomes and promoted action RNA-binding proteins G3BP1/2. granules have been implicated in several disease states, including cancer neurodegeneration. Consequently, compounds that limit stress or promote their dissolution potential as both experimental tools novel therapeutics. Herein, we describe two small molecules, G3BP inhibitor a b (G3Ia G3Ib), designed to bind specific pocket G3BP1/2 targeted viral inhibitors function. In addition disrupting co-condensation RNA, G3BP1, caprin 1 vitro, these inhibit cells treated prior concurrent with dissolve pre-existing granules. These effects are consistent across multiple cell types variety initiating stressors. Thus, represent powerful probe biology hold promise for therapeutic interventions modulate formation.

Language: Английский

Citations

22
Graphene Transistors for In Vitro Detection of Health Biomarkers DOI
Changhao Dai,

Derong Kong,

Chang Chen

et al.

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(31)

Published: May 10, 2023

Abstract Biomarkers are primary indicators for precise diagnosis and treatment. The early identification of health biomarkers has been sustained by the evolutionary success in sensor technologies. Among them, graphene field‐effect transistor (GFET) biosensors have exhibited major advantages such as an ultrashort response time, high sensitivity, easy operation, capability integration, label‐free detection. Owing to atomic thickness, restricts charge carrier flow merely at material surface responds foreign stimuli directly, leading effective signal acquisition transmission. Here, this review summarizes latest advances GFET a comprehensive manner that contains device design, working principle, functionalization, proof‐of‐concept applications. It provides survey with regard biomarker analysis single‐device level integrated prototypes include wearable sensors, biomimetic systems, healthcare electronics, diagnostic platforms. Moreover, there is discussion on long‐standing research efforts outlook future development systems from lab fab.

Language: Английский

Citations

25
A Functional Map of the Human Intrinsically Disordered Proteome DOI Creative Commons
Iva Pritišanac, T. Reid Alderson, Đesika Kolarić

et al.

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

Published: March 17, 2024

Abstract Intrinsically disordered regions (IDRs) represent at least one-third of the human proteome and defy established structure-function paradigm. Because IDRs often have limited positional sequence conservation, functional classification using standard bioinformatics is generally not possible. Here, we show that evolutionarily conserved molecular features intrinsically (IDR-ome), termed evolutionary signatures, enable prediction IDR functions. Hierarchical clustering IDR-ome based on signatures reveals strong enrichments for frequently studied functions in transcription RNA processing, as well diverse, rarely functions, ranging from sub-cellular localization biomolecular condensates to cellular signaling, transmembrane transport, constitution cytoskeleton. We exploit information encoded within conservation propose annotations every proteome, inspect correlate with different discover co-occurring scale. Further, identify patterns proteins unknown function disease-risk genes conditions such cancer developmental disorders. Our map should be a valuable resource aids discovery new biology.

Language: Английский

Citations

10
Biomolecular condensates in immune cell fate DOI
Srikanth Kodali, Caroline M. Sands, Lei Guo

et al.

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

Citations

1
Compartmentalization of multiple metabolic enzymes and their preparation in vitro and in cellulo DOI

Sayoko Ito‐Harashima,

Natsuko Miura

Biochimica et Biophysica Acta (BBA) - General Subjects, Journal Year: 2025, Volume and Issue: unknown, P. 130787 - 130787

Published: March 1, 2025

Language: Английский

Citations

1
Ion binding with charge inversion combined with screening modulates DEAD box helicase phase transitions DOI Creative Commons
Michael Crabtree, J. F. Holland, Arvind Pillai

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(11), P. 113375 - 113375

Published: Nov. 1, 2023

Membraneless organelles, or biomolecular condensates, enable cells to compartmentalize material and processes into unique biochemical environments. While specific, attractive molecular interactions are known stabilize repulsive interactions, the balance between these opposing forces, largely unexplored. Here, we demonstrate that electrostatic regulate condensate stability, internal mobility, interfaces, selective partitioning of molecules both in vitro cells. We find signaling ions, such as calcium, alter repulsions model Ddx3 Ddx4 proteins by directly binding negatively charged amino acid sidechains effectively inverting their charge, a manner fundamentally dissimilar screening. Using polymerization combined with generalized stickers spacers, accurately quantify predict stability over wide range pH, salt concentrations, sequences. Our provides general quantitative treatment for understanding how charge ions reversibly control stability.

Language: Английский

Citations

21
Calcium signaling from damaged lysosomes induces cytoprotective stress granules DOI Creative Commons

Jacob Duran,

Jaime Salinas-Chavira,

Rui Ping Wheaton

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Abstract Lysosomal damage induces stress granule (SG) formation. However, the importance of SGs in determining cell fate and precise mechanisms that mediate SG formation response to lysosomal remain unclear. Here, we describe a novel calcium-dependent pathway controlling formation, which promotes survival during damage. Mechanistically, calcium-activated protein ALIX transduces signals by eIF2α phosphorylation after sensing calcium leakage. enhances promoting association between PKR its activator PACT, with galectin-3 inhibiting this interaction; these regulatory events occur on damaged lysosomes. We further find plays crucial role upon caused factors such as SARS-CoV-2 ORF3a , adenovirus, malarial pigment, proteopathic tau, or environmental hazards. Collectively, data provide insights into mechanism implicate it diseases associated lysosomes SGs.

Language: Английский

Citations

7
Stress Granules as Causes and Consequences of Translation Suppression DOI
Max Baymiller, Stephanie L. Moon

Antioxidants and Redox Signaling, Journal Year: 2023, Volume and Issue: 39(4-6), P. 390 - 409

Published: May 15, 2023

Significance: Stress granules (SGs) are biomolecular condensates that form upon global translation suppression during stress. SGs enriched in factors and messenger RNAs (mRNAs), which they may sequester away from the protein synthesis machinery. While this is hypothesized to remodel functional transcriptome stress, it remains unclear whether a cause, or simply consequence, of repression. Understanding function particularly important because implicated numerous diseases including viral infections, cancer, neurodegeneration. Recent Advances: We synthesize recent SG research spanning biological scales, observing single proteins mRNAs within one cell measurements entire proteome population. use emerging understanding these studies suggest likely have less impact on translation, but instead strongly influence individual localized them. Critical Issues: Development unified model links stress-induced RNA-protein condensation regulation downstream gene expression holds promise for mechanisms cellular resilience. Future Directions: Therefore, upcoming should clarify what exert at all scales as well molecular enable this. The resulting knowledge will be required drive discovery how allow organisms adapt challenges support health go awry lead disease. Antioxid. Redox Signal. 39, 390–409.

Language: Английский

Citations

14
Time-resolved proteomic profiling reveals compositional and functional transitions across the stress granule life cycle DOI Creative Commons
Shuyao Hu, Yufeng Zhang, Qianqian Yi

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 27, 2023

Language: Английский

Citations

14