2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
March 7th, 2025
Version: 1
Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
biophysics
biorxiv

Deciphering the molecular mechanisms of FET fusion oncoprotein-DNA hollow co-condensates

Zuo, L.Open in Google Scholar•Guo, Q.Open in Google Scholar•Zhang, K.Open in Google Scholar•Jiang, B.Open in Google Scholar•Chen, Z.Open in Google Scholar•Xia, Y.Open in Google Scholar•Qian, L.Open in Google Scholar•Zhang, L.Open in Google Scholar•Qi, Z.Open in Google Scholar

Biomolecules such as nucleic acids and proteins can undergo liquid-liquid phase separation to form biomolecular condensates with diverse architectures. However, fundamental questions surrounding the biophysical principles that govern condensate architecture and their potential biotechnological applications remain unresolved. Here, we report that the FUS/EWS/TAF15 family fusion oncoprotein FUS-ERG forms hollow co-condensates with double-stranded DNA containing GGAA microsatellites. Through a combination of biochemical assays, super-resolution imaging, and mathematical modeling, we reveal that the interior surface of hollow co-condensates exhibits properties distinct from those of the external surface, a phenomenon we term nested asymmetric phase separation. Furthermore, we demonstrate that the self-organization and morphology control of FUS-ERG hollow co-condensates can be harnessed for DNA-based information manipulation, enabling targeted DNA deletion within dsDNA libraries and facilitating dynamic, hierarchical data selection. These findings provide critical insights into the biophysical mechanisms underlying multicomponent phase-separated cellular bodies and establish a foundation for leveraging condensate morphology in biotechnology.

Similar Papers

biorxiv
Fri Mar 07 2025
H2A.Z facilitates Sox2-nucleosome interaction by promoting DNA and histone H3 tail mobility
Epigenetic regulation of eukaryotic chromatin structure and function can be modulated by histone variants and post-translational modifications. The conserved variant H2A.Z has been functionally linked to pioneer factors Sox2 and Oct4 that open chromatin and initiate cell fate-specific expression programs. However, the molecular basis for their interaction remains unknown. Using biochemistry, nucle...
Moos, H. K.
•
Patel, R.
•
Flaherty, S. K.
•
Loverde, S. M.
•
Nikolova, E. N.
biorxiv
Fri Mar 07 2025
Electrostatics facilitate mid-air host attachment in parasitic jumping nematodes
Jumping can be hazardous for entomopathogenic nematodes (EPNs) as those that fail to attach to an insect host face death by predation or starvation. Recently, it has been shown that electrostatic charges on large insects can prompt a close-range detachment of free-living nematodes, which are non-parasitic and unable to jump. However, it remains unclear if static electricity can influence aerial in...
Ran, R.
•
Burton, J. C.
•
Kumar, S.
•
Bhamla, S.
...•
Ortega-Jimenez, V. M.
biorxiv
Thu Mar 06 2025
Transcriptional coregulation in cis around a contact insulation site revealed by single-molecule microscopy
Chromosome conformation in mammals is closely related to gene regulation. Within topologically associating domains, where genomic contacts are enriched, genes tend to show correlated expression across tissues and conditions, suggesting domain-wide mechanisms coregulating multiple genes, such as enhancer sharing or local histone mark spreading. At the single-cell level, where transcription occurs i...
Kerlin, M. A.
•
Aboulfath-Ladid, I.
•
Roensch, J.
•
Jaubert, C.
...•
Coulon, A.
biorxiv
Thu Mar 06 2025
Tension-Induced Stiffening of Cytoskeletal Components Regulates Cardiomyocyte Contractility
Cardiomyocytes continuously experience mechanical stimuli that regulate their contractile behavior and contribute to overall heart function. Despite the importance of mechanotransduction in cardiac physiology, the mechanisms by which cardiomyocytes integrate external mechanical cues, such as stretch and environmental stiffness, remain poorly understood. In this study, we present a combined theoret...
Jafari, M.
•
Datla, S.
•
Elson, E. L.
•
Carlson, B.
...•
Alisafaei, F.
biorxiv
Thu Mar 06 2025
T-cell receptor specificity landscape revealed through de novo peptide design
T-cells play a key role in adaptive immunity by mounting specific responses against diverse pathogens. An effective binding between T-cell receptors (TCRs) and pathogen-derived peptides presented on Major Histocompatibility Complexes (MHCs) mediate an immune response. However, predicting these interactions remains challenging due to limited functional data on T-cell reactivities. Here, we introduc...
Visani, G. M.
•
Pun, M. N.
•
Minervina, A. A.
•
Bradley, P. H.
...•
Nourmohammad, A.
biorxiv
Thu Mar 06 2025
Titin as a mechanical damper: Balancing Stability and longevity through inter-domain linker design
Titin, a giant protein (~3-4 MDa), functions as a molecular-spring to regulate muscle elasticity. More than 90% of Titin is composed of domains that absorb mechanical energy and undergo stochastic unfolding-refolding under tension (~tens of pN). These domains are connected in tandem by interdomain linkers (IDLs), which constitute less than 10% of the total mass. Despite their small genomic footpri...
RAKSHIT, S.
•
SAHA, P.
•
Joshi, T.
•
Bhati, G. K.
...•
Bisht, D.
biorxiv
Thu Mar 06 2025
Thermal Adaptation of Extremozymes: Temperature-Sensitive Contact Analysis of Serine Proteases
Enzyme thermal adaptation reflects a delicate interplay between sequence, structure, and dynamics of proteins, fine-tuning the catalytic activity to environmental demands. Understanding these evolutionary relationships can drive bioengineering advances, including industrial enzyme design, biocatalysts for extreme conditions, and novel therapeutics. This work explores sequence-dynamics connections ...
Kulathunga, D. P.
•
Potoyan, D.
biorxiv
Thu Mar 06 2025
Asymmetry and Heterogeneity in the Plasma Membrane
Plasma membranes (PMs) exhibit asymmetry between their two leaflets in terms of phospholipid headgroups, unsaturation, and resulting membrane properties such as packing and fluidity. Lateral heterogeneity, including the formation of lipid domains, is another crucial aspect of PMs with significant biological implications. However, the nature and even the existence of lipid domains in the two leafle...
Yamada, T.
•
Shinoda, W.
biorxiv
Thu Mar 06 2025
Predicting Biological Age Using an Accumulated Neurotoxicity Biomarker for Amyloid Beta Oligomers
This study proposes using accumulated neurotoxicity, defined as the time integral of A{beta} oligomer concentration, as a biomarker for neuronal aging. A relationship between biological age and accumulated neurotoxicity is proposed. Numerical analysis guided the development of a new analytical solution linking the biological and calendar ages of neurons. The effects of A{beta} monomer and oligomer...
Kuznetsov, A. V.