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In bacteria, many small regulatory RNAs (sRNAs) associate with the RNA chaperone Hfq to modulate gene expression at the post-transcriptional level. Here, the authors identify global Hfq-mediated RNA-RNA interactions in Caulobacter crescentus and uncover a sponge RNA that antagonizes four homologous sRNAs in response to carbon starvation.

Intelectin-2 defends mucosal interfaces by crosslinking mucus and blocking microbial growth. This study reveals that mouse and human intelectin-2 recognizes galactose-rich glycans to bind and target diverse bacteria—uncovering a potent, dual-action lectin that shapes host–microbe balance.

Cardiac fibrosis arises from persistent myofibroblast activity. This study reveals how chromatin factors control scar-forming cells in the heart and shows that inhibiting KAT5 can reduce harmful cardiac fibrosis.

Arrayed CRISPR libraries with each plasmid encoding an array of four non-overlapping single-guide RNAs allow for the efficient genome-wide ablation, activation and epigenetic silencing of human protein-coding genes.

Xenotransplantation of a genetically edited pig kidney with a thymic autograft into a brain-dead human for 61 days with immunosuppression resulted in stable kidney function without proteinuria, and xenograft rejection was treated and reversed by the end of the study.

Benito-Martínez, Salavessa and colleagues show that keratin intermediate filaments and microtubules control the three-dimensional perinuclear position of melanin-containing organelles, shielding the DNA from photodamage.

Silencing of transgenes such as Cas9 limits gene editing and CRISPRa applications. Here, the authors show that adding intronic sequences reduces silencing and boosts transgene expression, enabling improved CRISPRa-mediated gene activation and more stable expression of the transgene over time.

The majority of human genes can produce multiple isoforms, but studying their functional relevance requires tools to target specific isoforms. Here, the authors develop a CRISPR-based exon-exon junction-targeting strategy to achieve isoform-specific RNA knockdown.

Zamboni et al. reveal how enhancers encode cell-type-specific responses to CNS injury. By combining multiomic profiling, deep learning and in vivo screening, they uncover injury-responsive enhancer logic and enable targeting of reactive astrocytes.

Antibody discovery is bottlenecked by the individual expression and evaluation of antigen specific hits. Here, the authors build an antibody screening workflow leveraging cell-free protein synthesis that enables expression and evaluation of hundreds of antibody fragments in less than 24 h.

Metabolism plays an important role in response to DNA damage, however the underlying mechanisms are less clear. Here, the authors identify a non-canonical role of IMPDH2 wherein it is recruited to the chromatin following DNA damage and mediates PARP1-dependent DNA damage repair via the regulation of nuclear NAD+ levels.

Many bacteria use the second messenger cyclic diguanylate (c-di-GMP) to control motility, biofilm production and virulence. Here, the authors identify a thermosensitive enzyme that synthesizes c-di-GMP and modulates temperature-dependent motility, biofilm development and virulence in the opportunistic pathogen Pseudomonas aeruginosa.

The ATPase UAP56 acts as an ATP-gated molecular switch that directs mRNA ribonucleoprotein complexes from TREX to nuclear-pore-complex-anchored TREX-2 complexes for mRNA export from the nucleus.

Ring deconvolution microscopy leverages symmetry to provide fast and straightforward spatially varying deblurring and offers improved speed and image quality compared to standard approaches across diverse microscopy modalities.

The ferroptosis suppressor protein FSP1 has a critical role in ferroptosis protection of tumours across multiple in vivo models and is linked to worse prognosis in human lung adenocarcinoma, suggesting its potential as a therapeutic target in lung cancer.

The nuclear localization of metabolic enzymes is fascinating and in most cases remains a mystery. Here, Pardo Lorente and colleagues show that nuclear MTHFD2 is required for successful mitosis by controlling centromeric histone methylation.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Using a multi-OMICS approach, Haas et al identify 54 human genes and 16 host-targeting chemical compounds that regulate influenza A virus infection in lung epithelial cells, including AHNAK and COBP1 which are also essential for SARS-CoV-2 infection.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

In this work, authors show that β-lactamase enzymes not only confer antibiotic resistance but also increase susceptibility to other antibiotics.

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

Xu et al. identify REPRODUCTIVE MERISTEM transcription factors that are required for RNA-directed DNA methylation at CLASSY3 target loci in male and female reproductive tissues of Arabidopsis.

Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.

The identification of processes activated by specific microbes during microbiota colonization of plant roots is hampered by technical issues in metatranscriptomics. Here, Vannier et al. colonized germ-free plants with a defined root microbiota comprising over 100 microbial isolates, and addressed those issues in various ways to identify strain-specific processes as well as common gene sets activated by microbes during root colonization.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Global ocean microbiome survey reveals the bacterial family ‘Candidatus Eudoremicrobiaceae’, which includes some of the most biosynthetically diverse microorganisms in the ocean environment.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

ESCAPE-seq (enhanced single-chain antigen presentation sequencing) is a massively parallel platform for screening of class I HLA–peptide combinations for antigen presentation. The authors assess more than 75,000 peptide–HLA combinations, revealing presented epitopes from oncogenic driver mutations and fusions across diverse HLA-A, HLA-B and HLA-C alleles.

Mass spectrometry and structural studies demonstrate the specific changes in protein composition that accompany the transition of ribosomes in zebrafish and Xenopus eggs from a dormant to an active state during early embryogenesis.

Mauthe et al. find that protein aggregate clearance requires fragmentation of the aggregate by a chaperone module and a proteasomal regulatory particle for recruitment and clustering of selective autophagy receptors to initiate phagophore formation.

Pioneer neurons extend their axons to provide a track for follower neurons to follow, whether these neurons differ in other ways has not been clear. Here they show that pioneer and follower neurons are transcriptionally distinct and that RA signaling is required for pioneer axon targeting.

In this study, Tai et al. provide insights into the metabolic and bioenergetic responses in the axonal compartment in the context of multiple sclerosis. Moreover, they show how upregulating the tricarboxylic acid cycle confers protection against neuroinflammation-induced energy deprivation.

Characterization of bacterial auxin degradation loci and their regulators reveals two distinct types across plant microbiome species, where only one, exemplified in Variovorax species, can interfere with root growth inhibition in a complex synthetic microbial community.

The authors describe a new crosstalk between a globally disseminated carbapenem resistance plasmid and clinical enterobacteria clones. This crosstalk provides a fitness advantage to the plasmid-carrying bacteria, promoting the spread of resistance.

By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding interdomain misfolding.

Analysis of 4,041 single-nucleotide variants (SNVs) linked to 13 cancers performed in primary human cell types identifies 380 potentially regulatory SNVs and their putative target genes. Editing one SNV, rs10411210, revealed that the risk allele increases RHPN2 expression and stimulus-responsive RhoA activation.

BindCraft, an open-source, automated pipeline for de novo protein binder design with experimental success rates of 10–100%, leverages AlphaFold2 weights to generate binders with nanomolar affinity without the need for high-throughput screening.

The authors show that loss-of-interaction with the nuclear importer, TNPO3, causes cytoplasmic mislocalization of RBM20 variants linked to severe cases of dilated cardiomyopathy. Restoring their nuclear localization alleviates the disease phenotype.

DNA transactions promote torsional constraints that pose inherent risks to genome integrity. Here the authors identify the macro-histone splice variant macroH2A1.1 as an epigenetic modulator of topoisomerase 1-associated genome maintenance. MacroH2A1.1 expression determines sensitivity to TOP1 poisons and may present a cancer vulnerability.

Tim17 contains conserved negative charges close to the intermembrane space side of the bilayer, which are essential to initiate presequence protein translocation along a distinct transmembrane cavity of Tim17 for both classes of preproteins.

Prior to anaphase, securin binds separase and thereby prevents cohesin cleavage. Here, the authors develop a method to produce active securin-free separase, identify a docking motif in cohesin that promotes cleavage, and show that securin interferes with this interaction.

Comprehensive CRISPR mutagenesis targeting all members of the NuRD complex identifies a specific subcomplex required for fetal globin silencing and informs a rational targeting strategy for elevating globin levels while avoiding cytotoxicity.

Autonomous hypermutation yeast surface display (AHEAD) mimics the process of somatic hypermutation in animals to enable the rapid in vitro evolution of antibodies, including nanobodies targeting the RBD of SARS-CoV-2.

A combination of analysis of plasmid diversity in the gut of hospitalized patients with experimental evolution shows that the evolution of plasmid-mediated antibiotic resistance involves a trade-off between antibiotic resistance levels and bacterial fitness.

Cytokinesis in budding yeast is accompanied by a major rearrangement of septins into a double ring. Here, authors show that the F-BAR protein Hof1 contributes to septin remodeling upon its phosphorylation and relocalisation from septins to the division site.