In nuclear speckles, sequence-encoded inter-domain attractive and repulsive interactions drive proteins to form hierarchical structures, including size-limited microphases, clusters of microphases, micron-scale double emulsions in protein mixtures, and microphases stabilized by preferential and protein-specific binding to the lncRNA MALAT1.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitatin...

Grammars inferred using NARDINI+ (GIN) is a resource that uncovers molecular grammars of intrinsically disordered regions (IDRs) across the human proteome, revealing how distinct grammars underlie pro...

By sidestepping Cas9 immunogenicity, the StealTHY CRISPR platform enables immune-compatible in vivo genetic screens, directly translatable to humanized cancer models. Using this immune-stealth strateg...

Phase separation stabilizes synthetic gene circuits and boosts production under dynamic growth conditions. By locally concentrating transcription factors at promoters, it protects gene expression from...

Distinct phosphorylation marks are placed on the carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) during different stages of gene transcription. These phospho-CTD marks function as a molec...

Upon DNA breakage, a genomic locus undergoes alterations in three-dimensional chromatin architecture to facilitate signaling and repair. Although cells possess mechanisms to repair damaged DNA, it is ...

Stem cell differentiation is controlled by manipulating RNA condensates.

Live-cell imaging of mRNA encoding secretome proteins and translated nascent peptide markers show that secretome translation occurs at endoplasmic reticulum junctions near lysosomes, requires lun...

The formation of condensates by the Linker for the Activation of T-cells (LAT) is a key signal gating and amplification step in the T-cell receptor signaling pathway. LAT condensation is challenging t...

MAGE is a sequence-based protein language model designed to generate diverse human antibody sequences targeting various pathogens, including SARS-CoV-2, H5N1, and RSV-A. This AI-driven approach addres...

This study reveals how a cancer-associated mutation in CHD1 leads to the loss of its C-terminal intrinsically disordered region, disrupting condensate formation. This impairment causes improper genome...

Analysis of the longest-lived mammal, the bowhead whale, reveals an improved ability to repair DNA breaks, mediated by high levels of cold-inducible RNA-binding protein.  &nbs...

Phenotypic drug screening remains constrained by the vastness of chemical space and technical challenges scaling experimental workflows. To overcome these barriers, computational methods have been dev...

Studies of the G-protein-coupled receptor NTSR1 show that the G protein selectivity of this receptor can be modified by small molecules, enabling the design of drugs that work by switching receptor su...

Ants evolved a transcriptional-interference-based mechanism to express a single odorant receptor from an array of Or genes with functionally similar promoters.

The capacity of biomolecular condensates to establish and modulate electrochemical equilibria is emerging as an important functioning mechanism in cellular biochemistry. However, the physical chemistr...

This study introduces single-cell transcription factor (TF) sequencing, a single-cell barcoded and doxycycline-inducible TF overexpression approach that reveals dose-sensitive functional classes of TF...

This study introduces single-cell transcription factor (TF) sequencing, a single-cell barcoded and doxycycline-inducible TF overexpression approach that reveals dose-sensitive functional classes of TF...

Optical nanoscopy of intact biological specimens has been transformed by recent advancements in hydrogel-based tissue clearing and expansion, enabling the imaging of cellular and subcellular structure...

Synaptic vesicle (SV) exocytosis underpins neuronal communication, yet its nanoscale dynamics remain poorly understood owing to limitations in visualizing rapid events in situ. Here, we used optogenet...

Protein complexes are essential for cell function. Here, authors show that paired ribosomes can help each other’s nascent chains fold correctly, enabling proper dimer assembly and preventing misfolding, using lamin as a model system.

This study presents FolTAC-dual, a folate receptor-mediated platform for dual degradation of EGFR/HER2 and PD-L1/VISTA, offering a strategy to overcome drug resistance and enhance antitumor immunity for cancer treatment.

Pronobis et al. show that Ddx61 localizes to P-bodies and regulates heart muscle proliferation during cardiac regeneration in zebrafish. Ddx61 is required is required to restrain expression of Chordin, a secreted BMP inhibitor that impedes regeneration if present at high levels.

From a regulatory T cell surprise to a long-awaited honor for metal-organic frameworks, scientists shared their thoughts on this year’s award-winning research.

This study introduces single-cell transcription factor (TF) sequencing, a single-cell barcoded and doxycycline-inducible TF overexpression approach that reveals dose-sensitive functional classes of TFs and cellular heterogeneity by mapping TF dose-dependent transcriptomic changes during the reprogramming of mouse embryonic multipotent stromal cells.

Phase-separated condensates selectively enrich a wide range of molecules and regulate their properties, playing essential roles in cellular functions …

This study shows that p300/CBP-dependent H2B acetylation is crucial for maintaining transcription of oncogenic gene programs in androgen receptor-driven prostate cancer.

Zhang et al. delineate the heterogeneity of core regulatory circuitry in glioblastoma and identify HOXB3 condensation as a vulnerability that may be targeted with a therapeutic peptide in mouse models.

Wang, He, Gong and colleagues identify an age-related decline in the palmitoyltransferase ZDHHC11 in chondrocytes that leads to senescence and the pathogenesis of osteoarthritis, highlighting the potential of targeted ZDHHC11 delivery as a therapeutic strategy for osteoarthritis.

Protein secondary structures are visualized in situ by hyperspectral stimulated Raman scattering microscopy, revealing disordered to ordered changes in protein phase separation and structural heterogeneity of subcellular aggregates in live cells.

Recent breakthroughs in spatial transcriptomics technologies have enhanced our understanding of diverse cellular identities, spatial organizations, an…

Tau aggregation, a hallmark of Alzheimer’s disease, disrupts neuron structure. Aging weakens chaperone defenses like Hsp90. This study designs β-Hsp90, a small peptide mimicking Hsp90, to prevent Tau aggregation, offering promise for new amyloid disease drugs.

Adenosine triphosphate (ATP)–dependent chromatin remodeling enzymes mobilize nucleosomes, but how such mobilization affects chromatin condensation is unclear. We investigate effects of two major remod...

A proteotoxic stress response specific to exhausted T cells, governed by AKT signaling and accompanied by increased protein translation, represents a mechanistic vulnerability and a new therapeutic target to improve cancer immunotherapies.

An analysis of T cell responses in people with amyotrophic lateral sclerosis shows that the C9orf72 antigen is a key target of autoimmune responses in the disease, and identifies C9orf72 epitopes that are recognized.

Heterochromatin Protein 1α (HP1α) is a fundamental component of constitutive heterochromatin, forming subnuclear condensates whose regulation and function remain poorly understood. Here, we present an...

Here the authors show that LC3-associated phagocytosis is initiated by various receptors, which enrich phosphatidylserine in the membrane domains proximal to the phagosome, recruiting Rubicon to the membrane for phagosome maturation.

Nature Structural & Molecular Biology, Published online: 22 September 2025; doi:10.1038/s41594-025-01659-6Many mutations cause disease because they destabilize proteins. Here, Mighell and Lehner show that a single small molecule can correct the destabilization caused by nearly all pathogenic mutations in a human GPCR.

Leder et al. show that the chaperones PDIA6, Hsp70 BiP, ERdj3, PDIA1 and Hsp90 form co-condensates within the endoplasmic reticulum, enhancing folding and preventing misfolding of client proteins.

Using computational and experimental methods, Ouyang and Chen et al. reveal a drug design principle that the hydrophobic properties of small-molecule drugs significantly influence their ability to eng...

Nuclear biomolecular condensates are functional sub-compartments within the cell nucleus. Here, the authors develop a synthetic DNA protonucleus that enables RNA transcription and condensation into di...

A screen for protein degraders discovers hits by imaging cell survival.

Biomolecular condensates are made of multiple components but current techniques cannot capture their complex composition quantitatively. Now it has been shown that the dense-phase binodal point defini...

Zhu et al. reveal that TEAD transcription factors form nuclear condensates that recruit endogenous YAP/TAZ. These condensates act as dynamic hubs for enrichment of TEAD regulators and provide a framew...

A new method enables comprehensive screening and identification of low-affinity DNA binding sites for transcription factors, and reveals that nucleotides flanking high-affinity binding sites create ov...