Acta Biochimica et Biophysica Sinica, Journal Year: 2023, Volume and Issue: 55(7), P. 1021 - 1022
Published: July 1, 2023
Language: Английский
Deleted Journal, Journal Year: 2025, Volume and Issue: 2(1)
Published: Jan. 1, 2025
Human antigen R (HuR) is a ubiquitously expressed RNA-binding protein (RBP) that has been implicated in vast range of biological processes including stress response, angiogenesis, cell proliferation, and differentiation. Dysregulation HuR linked to number pathological disorders vascular disease, inflammation, cancers such as those the breast colon. Like many RBPs, composed multiple RNA-recognition motif (RRM) domains; however, three other members Hu family (HuB, HuC, HuD) possess unique structural composition with two RRMs separated from third C-terminal RRM by long, unstructured hinge region. While there extensive research on role cellular, molecular, developmental biology, are fewer biochemical studies questions still remain about molecular mechanisms HuR. In this review, we endeavor synthesize existing spanning last decades order define known mechanistic roles each domain, highlight remaining uncertainties, provide backdrop for ongoing into chemistry biology similar multi-RRM containing proteins.
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1356 - 1356
Published: Feb. 5, 2025
Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA-binding protein containing low-complexity domains (LCDs), which are known to regulate behavior under stress conditions. This study demonstrates the ability control hnRNPK’s transitions into four distinct material states—monomer, soluble aggregate, liquid droplet, and fibrillar hydrogel—by modulating environmental factors such as temperature concentration. Importantly, phase-separated hydrogel states newly identified for eGFP-hnRNPK, marking a significant advancement in understanding its properties. A combination of biophysical techniques, including DLS SEC-LS, were used further characterize hnRNPK monomeric aggregate states. Structural methods, SANS, SAXS, TEM, revealed elongated morphology monomer. Environmental perturbations, decreased or crowding agents, drove gel-like states, each with characteristics. These novel analyzed using SEM, X-ray diffraction, fluorescence microscopy. Collectively, these results demonstrate complex behaviors different conditions illustrate properties state. Transitions upon condition changes could potentially affect functions hnRNPK, playing role regulation hnRNPK-involved processes cell.
Language: Английский
Citations
0
Nature Structural & Molecular Biology, Journal Year: 2025, Volume and Issue: unknown
Published: May 2, 2025
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 7, 2025
SUMMARY PTK2, a non-receptor tyrosine kinase, is essential for regulating pivotal cellular functions, including survival by reducing p53 levels and activating PI3K/AKT pathway. However, the mechanism underlying PTK2 stabilization during stress remained unclear. Here, we identified Bclaf1, multifunctional protein known to stabilize partners, as interactor. Using advanced microscopy techniques, nuclear Bclaf1 biomolecular condensates containing in cardiomyocytes under oxidative stress. While diffused through nucleus was susceptible ubiquitination, sequestered protected from ubiquitin-proteasome system (UPS). The ubiquitination site K926 identified, proteasome inhibition confirmed UPS role homeostasis. Furthermore, disruption of culminates degradation, ultimately increasing apoptosis. Our findings support driving formation pro-survival that sequester promoting cardiomyocyte
Language: Английский
Citations
0
Cell Reports, Journal Year: 2024, Volume and Issue: 43(8), P. 114617 - 114617
Published: Aug. 1, 2024
Liquid-liquid phase separation (LLPS) mediated by G3BP1/2 proteins and non-translating mRNAs mediates stress granule (SG) assembly. We investigated the phylogenetic evolution of G3BP orthologs from unicellular yeast to mammals identified both conserved divergent features. The modular domain organization is generally conserved. However, invertebrate displayed reduced capacity for SG assembly in human cells compared vertebrate orthologs. demonstrated that protein-interaction network facilitated NTF2L a crucial determinant this specificity. G3BP1 coincided with its exploitation certain viruses, as evident interaction between viral insects vertebrates. revealed importance divergence formation. Leveraging network, we established 7-component vitro reconstitution system quantitative studies. These findings highlight significance biological processes.
Language: Английский
Citations
1
Biophysical Reviews and Letters, Journal Year: 2024, Volume and Issue: 19(01), P. 1 - 16
Published: March 1, 2024
A key biophysical process in biological systems, liquid–liquid phase separation (LLPS) is responsible for constructing membrane-less organelles and modulating cellular activities. The mechanisms underlying LLPS are explored this paper, with an emphasis on multivalent interactions, entropy-driven processes, how they affect organization. We investigate the impact of external stimuli behavior clarify physiological roles biomolecular condensates, from stress response modulation to gene expression regulation. In addition, we study dysregulated human disorders, providing information about possible therapeutic targets approaches innovative therapeutics. Through interdisciplinary approach, aim improve our knowledge its effects health illness, opening door new that focus proteins structure cells.
Language: Английский
Citations
1
Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 26, 2024
Understanding of the physicochemical properties and functions biomolecular condensates has rapidly advanced over past decade. More recently, many RNA viruses have been shown to form cytoplasmic replication factories, or viroplasms, via phase separation their components, akin numerous cellular membraneless organelles. Notably, diverse from Reoviridae family containing 10–12 segmented double-stranded genomes induce formation viroplasms in infected cells. Little is known about inner workings these inclusions how they may support stoichiometric assembly with genomes, raising questions roles coordinating viral genome packaging. Here, we discuss molecular composition determines properties, highlighting interplay between structure, remodelling, condensate self-organisation. Advancements structural probing theoretical modelling can reveal mechanisms through which ribonucleoprotein complexes selective enrichment distinct RNAs.
Language: Английский
Citations
1
Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(43)
Published: Oct. 17, 2024
Liquid–liquid phase separation has emerged as a crucial mechanism driving the formation of membraneless biomolecular condensates, which play important roles in numerous cellular processes. These found both nucleus and cytoplasm, are formed through multivalent, low-affinity interactions between various molecules. P62-containing condensates serve, among other functions, proteolytic hubs for ubiquitin–proteasome system. In this study, we investigated dynamic interplay nuclear p62 promyelocytic bodies (PML-NBs). We show that stabilize PML-NBs under basal conditions following exposure to arsenic trioxide stimulates their degradation. further effect on stability is due sequestration ubiquitin E3 ligase RNF4 with subsequent rapid degradation ligase. The made possible by association proline-rich domain PML protein PB1 p62, results PML-NB shell around condensates. Importantly, these hybrid structures do not undergo fusion mixing contents leaves unsolved findings suggest an additional tumor suppressor mediated via different
Language: Английский
Citations
1
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12950 - 12950
Published: Dec. 2, 2024
Stress granules (SGs) are membrane-less aggregates that form in response to various cellular stimuli through a process called liquid-liquid phase separation (LLPS). Stimuli such as heat shock, osmotic stress, oxidative and infections can induce the formation of SGs, which play crucial roles regulating gene expression help cells adapt stress conditions. Various mRNAs proteins aggregated into particularly those associated with protein translation machinery, frequently found SGs. When induced by infections, SGs modulate immune cell activity, supporting against infection. The differ viral versus microbial depending on type involved, function differently In this review, we summarize our current understanding implication immunity organelles context infectious diseases. Importantly, explore insights regulatory functions host under
Language: Английский
Citations
1
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown
Published: Dec. 11, 2023
Abstract PIWI-interacting RNAs (piRNAs) are essential for maintaining genome integrity and fertility in various organisms. In flies nematodes, piRNA genes encoded heterochromatinized genomic clusters. The molecular mechanisms of transcription remain intriguing. Through unique indexed-small RNA sequencing chromosome editing, we discovered that spatial aggregation enhances their nematodes. recruits the complex USTC (including PRDE-1, SNPC-4, TOFU-4, TOFU-5) H3K27me3 reader UAD-2, which phase separate into droplets to initiate transcription. We searched factors regulate condensate formation isolated SUMO E3 ligase GEI-17 as inhibiting protease TOFU-3 promoting formation, thereby regulating production. Our study revealed genes, separation deSUMOylation may benefit organization functional biomolecular condensates direct genome.
Language: Английский
Citations
2