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This study discovers human SERF2 as a key partner in stress granule formation by binding specific RNA G-quadruplexes. SERF2 and these RNAs provide a detailed structural model of protein-RNA interactions driving liquid-liquid phase separation in condensates.

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.

Engineering motif-specific 'hot spots' into an antibody scaffold yields antibodies with high affinity to targets containing phosphoserine, phosphothreonine or phosphotyrosine.

Proteome allocation to anabolic and catabolic functions is significantly regulated by growth rate in the model bacterium Escherichia coli. By contrast, this article shows that proteome allocation is only partially controlled by growth rate, and metabolic rates are primarily controlled post-translationally, in the thermophilic acetogen Thermoanaerobacter kivui.

Khetarpal et al. show that the metabolic regulator PGC-1α is essential in heart muscle cells for exercise-driven cardiac growth, and that suppression of the stress-induced myokine GDF15 is required to enable cardiomyocyte adaptations to training.

Khan et al. report a non-catalytic function of the methyltransferase SETD2 in regulating nuclear morphology and genome integrity. The SETD2 amino terminus functions as a scaffold helping CDK1 associate with lamins during nuclear-envelope disassembly

The barrier function of skin epidermis requires polarized secretion of lamellar bodies towards the body surface. Here, Rudd et al. identify Flower (FWE) as a novel regulator of lamellar body trafficking and a determinant of epidermal barrier function.

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

Boccella, Yu and colleagues reveal that the transmembrane protein ANTXR1 regulates post-infarction fibrotic remodeling, and its inhibition blocks collagen turnover and improves heart function.

Lekkos et al. show that a metabolic switch toward oxidative phosphorylation is required for cardiomyocyte re-differentiation and heart regeneration after injury in fish.

Translocation renal cell carcinoma (tRCC) is driven by MiT family gene fusions. Here, the authors demonstrate that RNA-binding features of TFE3 fusions facilitate condensate formation, promoting transcriptional hub assembly and oncogenic gene activation.

In this work, authors utilise comparative transcriptomics to reveal lncRNAs that distinguish pathogen-specific from core macrophage responses. They identify a Q fever-specific AHR-regulated CYP1B1-AS1/CYP1B1 axis that modulates mitochondrial homeostasis and survival of Coxiella burnetii.

Oncolytic virus holds potential as a cancer therapy, but further optimization is desirable. Here the authors screen existing drug to find talazoparib, a PARP inhibitor, synergizing with reovirus type 3 Dearing (RT3D) to induce cancer cell apoptosis, anti-tumor immunity, as well as control of primary and rechallenge tumor in mouse models.

Using metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma mouse models, an ATP citrate lyase inhibitor reduces tumour burden and enhances efficacy of current standards of care.

Jansen et al. determined the cryo-electron microscopy structure of human GTPase-activating protein complex GATOR2 bound to CASTOR1 in the absence of arginine, providing insight into how CASTOR1 binds to GATOR2 to disinhibit GATOR1 when arginine levels are low, promoting mechanistic target of rapamycin complex 1 inactivation.

Cangkrama et al. show that tumor cells from various cancer types use the mitochondrial trafficking protein MIRO2 and nanotubes to transfer mitochondria into surrounding fibroblasts, thereby inducing cancer-associated fibroblast differentiation and subsequent tumor growth.

Although IWS1 has been implicated in transcription-coupled processes, its direct role in RNA polymerase II function remained undefined. Here, the authors demonstrate that IWS1 enhances Pol II elongation velocity by acting as a structural scaffold and promoting co-transcriptional H3K36me3 deposition.

Lineage switching (LS) facilitates acute myeloid leukemia (AML) escaping CD19 targeted immunotherapy, but the underlying mechanism are not well understood. The authors here analyze patients’ single-cell mass cytometry and single-cell transcriptomics data, and identify an LS AML with the MDSC-like phenotype which is associated with LS in AML with KMT2A rearrangement.

Cottam et al. identify distinct pathways for D-ribulose utilisation in pathogenic Escherichia coli and Citrobacter rodentium, providing mechanistic details and suggesting convergent evolution towards utilisation of this nutrient in nature.

Glutarate rewires cell metabolism through conjugation to proteins or fatty acids, but how glutarylation is regulated is unclear. ABHD11 was identified as a lipoyl-deglutarylase to maintain the TCA cycle and mitochondrial metabolism.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Sensitive diagnostics are needed to detect carcinogenic human liver fluke infections. Sadaow et al. here use an immunomics approach to develop field-deployable tests for diagnosing liver fluke infection and its associated liver cancer.

We present a protocol for the analysis of polar and ionic metabolites by using anion-exchange chromatography–tandem mass spectrometry (AEC-MS/MS) with an untargeted or semi-targeted workflow for the identification of metabolites in biological samples.

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

Human gut bacteria bioaccumulate per- and polyfluoroalkyl substances (PFAS), commonly known as forever chemicals, in intracellular aggregates. Colonization of gnotobiotic mice with bioaccumulating bacteria increases faecal PFAS excretion.

SERPINB9 (SPB9) has been reported as a critical factor in the resistance to immunotherapy but its role in chemosensitivity remains unknown. Here this work reports that gemcitabine (GEM) treatment leads to upregulation of SPB9 in vitro/vivo, therefore engineer a nanocarrier co-delivering GEM and siSPB9 for preclinical pancreatic cancer treatment.

Lipoprotein uptake dependent on sulfated glycosaminoglycans linked to cell-surface proteoglycans is a key determinant of ferroptosis sensitivity in cancer.

The antiviral dsRNA sensor PKR is regulated by PACT. This paper shows how PACT prevents aberrant PKR activation by endogenous dsRNAs like Alu. PACT disrupts PKR’s dsRNA scanning without blocking its binding, resetting its activation threshold to tolerate cellular dsRNA and preserve homeostasis.

Design of cysteine-targeting analogs of a reversible SETDB1 triple Tudor domain (3TD) ligand, UNC6535, led to UNC10013, a potent covalent ligand with high selectivity. UNC10013 demonstrated allosteric inhibition of SETDB1-mediated Akt methylation in cells, a promising approach to SETDB1 therapeutics.

Here the authors use modified RNA and VHH libraries to generate intrabodies that target dysregulated interactions between two calcium handling proteins in failing cardiomyocytes. Heart specific expression of the intrabodies in a murine heart failure model results in improved cardiac function.

Truncated version of adenylyl cyclase 3 acts as a cold-induced rheostat during long-term brown adipose tissue activation.

The receptor-like kinase NIK1 is phosphorylated in response to multiple biotic and abiotic signals, activating the NIK1/RPL10/LIMYB signaling circuit, which coordinately regulates translation and photosynthesis in response to environmental changes.

The broad neuraminidase-specific influenza neutralizing monoclonal antibody binds the active site in a manner that accommodates the recently acquired Asn245 glycosylation and mimics the substrate sialic acid.

By regulating the level of accessible cholesterol on endothelial cells via OSBP/ORP-mediated transport, tetraspanin tunes the balance of Cdc42 and RhoA activities to affect vascular inflammation. Reducing accessible cholesterol by statin treatment or blocking its non-vesicular transport by OSBP/ORP inhibition can limit vascular inflammation.

Adriaenssens et al. show that unlike soluble cargo receptors, transmembrane cargo receptors initiate autophagosome biogenesis by recruiting the FIP200/ULK1 or WIPI–ATG13 complex, revealing unexpected flexibility in the selective autophagy machinery.

Different phosphorylation patterns created by GRK2 and GRK5 on the C-terminal tail of ACKR3 lead to distinct structural arrangements and dynamics of G-protein-coupled receptor–arrestin complexes, potentially explaining diverse cellular outcomes.

Authors show that the MKP5 phosphatase domain – required for catalysis – contains an allosteric site maintained by key hydrophobic residues, and this allosteric pocket binds MAPK which induces conformational changes that promote MAPK dephosphorylation.

End-of-life nonhuman primates can be used to screen pools of lipid nanoparticles for clinical safety studies.

Motif grammar on nucleosome fibres acts as signpost elements, directing TF combinatorial binding to enhancers.

Bacterial large subunit assembly is rapid and intricate, involving complex RNA domain interactions. Here, authors use anti-sense oligonucleotide probing with cryo-EM to reveal early-stage domain consolidation and identify RNA foldons that guide late-stage assembly.

The rise in highly pathogenic avian influenza cases elevates the risk of human-to-human transmission. Here, the authors develop an adjuvanted protein-based vaccine that elicits robust antibody- and cell-mediated immune responses in mice and non-human primates, suggesting its potential to induce protective immunity in humans.

Here the authors show that human pancreatic islets adapt during pregnancy with increased α-cell area and GLP-1 abundance, while key differences from islet adaptations in mouse pregnancy include unchanged β-cell PRLR abundance and absent β-cell 5-HT_2B receptor expression.

An adipocyte-selective product of the Clstn3 locus (CLSTN3β) facilitates the use of stored triglyceride by limiting lipid droplet (LD) expansion, defining a molecular mechanism that regulates LD form and function to facilitate lipid utilization in thermogenic adipocytes.

Cui et al. find that arginine depletion and inflammation reduces nuclear localization of arginyl-tRNA synthetase, which influences alternative splicing via condensate-like serine/arginine repetitive matrix protein 2, and regulates cellular metabolism and response to inflammation.

Chromosomes are coated in proteins and RNA called the mitotic chromosome periphery. Here, broadband microrheology analysis has shown that this coat has dynamic, liquid-like properties and provides an external structural constraint.

Daly, Danson and colleagues employ a multi-omic approach in neuroglioma cells to characterise endolysosomal dysfunction caused by perturbation of the evolutionarily conserved Retromer complex, highlighting Retromer’s neuroprotective function.

Ataxia-telangiectasia mutated protein (ATM) phosphorylates CD98HC to promote neutral amino acid antiporter trafficking. Here the authors show that ATM loss impairs glutamate, cystine, and arginine transport, driving metabolic stress and ataxia telangiectasia–like phenotypes.