Search

Prime assembly can initiate Gibson-like assembly in cells to generate gene insertions without double-stranded DNA breaks, recombinases or homology-directed repair.

Rapid methods to identify antigen-specific T cells are essential for developing targeted immunotherapies. Here the authors present a high-throughput MHC class II single-chain trimer platform for the comprehensive profiling of CD4⁺ T cells, enabling the rapid identification and characterization of virus- and tumour-specific T cell receptors (TCR) at single-cell resolution.

Researchers designed two-component proteins forming quasisymmetric cages via geometric frustration, enabling tunable virus-like assemblies for cargo delivery, cellular uptake and studying intracellular diffusion and protein localization.

Singh et al. combine cryo-electron microscopy and functional studies to reveal how a single protein complex selects diverse mRNAs for subcellular localization using a combination of shape, positional sequence information and number of structured RNA elements.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

Large-scale combinatorial perturbation screens are important to identify genetic interactions and synthetic lethal gene pairs. Here, Burgold et al. present a next-generation dual guide system that allows library-scale screening across hundreds of thousands of genetic interactions.

The anti-CRISPR protein AcrVA2 specifically interrupts Cas12a biogenesis by triggering co-translational mRNA degradation.

Bioinformatic, structural and functional analyses characterize Streptomyces antiquus insecticidal protein (SAIP) as a diphtheria toxin homologue that is lethal to insect cells and targets the Flower protein as a receptor

A vaccination strategy using heterologous HIV Env trimers covalently coupled to liposomes for multivalent display generates cross-neutralizing HIV serum antibody responses in non-human primates, mimicking infection-elicited apex-targeting broadly neutralizing antibodies.

mRNA vaccine efficacy is enhanced by silencing cell-type-specific expression.

Parkinson’s disease is managed through co-treatment with levodopa and tolcapone, with tolcapone altering the microbiome to increase its capacity to metabolize levodopa, implicating the gut microbiome in drug–drug interaction.

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.

PerturbFate is a high-throughput, cost-effective, single-cell platform that systematically profiles CRISPR interference perturbations to reveal common regulatory nodes and convergent phenotypic states across diverse genetic alterations linked to vemurafenib resistance in melanoma cells.

RNA base-editors are often used in methods for RNA binding protein (RBP) target discovery. Here the authors present a new RBP target discovery method, PRINTER, and suggest optimal RNA base-editors for dual-RBP studies, emphasizing the importance of matching rBEs’ editing biases with RBPs’ binding preferences.

Photoinduced ligand-to-metal charge transfer is used to enable abiotic cross-couplings in metalloenzymes. Engineering a 2-histidine metal site and substituting iron with nickel activates PsEFE for nickel-catalysed C(sp²)–S coupling reactions between thiols and aryl bromides. Directed evolution yielded metalloenzyme variants that can produce a range of thioethers with high efficiency.

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.

Memory is a basic tenet of intelligent biological systems. Here the authors engineered a programmable and expandable iteration of recombinase-based synthetic memory (interception) that functions post-translation, resulting in faster recombination.

A natural product containing an acylsulfenic acid functional group was discovered in a marine Streptomyces bacterium. Its biosynthesis is orchestrated by enzymes from both primary and secondary metabolism, including a flavin-dependent S-hydroxylase. The prevalence of enzymes catalysing the production of acylsulfenic acid in bacteria implies a potentially broad distribution of this functional group in specialized metabolites.

Here, the authors elucidate TMPRSS2 protease recognition of the SARS-CoV-2 spike S₂′ cleavage site, revealing the molecular basis of activation of membrane fusion, and show that antibodies recognizing the S₂′ site or TMPRSS2 block viral entry by interfering with TMPRSS2 access.

Saturation genome editing of a cancer mutation hotspot in CTNNB1, the gene encoding β-catenin, reveals a gradient of effects of missense mutations on Wnt signaling.

Improved red and green indicators for norepinephrine and their characterization are reported. These indicators allow detection of norepinephrine release in awake behaving mice in dual-color fiber photometry and two-photon imaging applications.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

Mammalian recombination activating genes RAG1 and RAG2 are essential for the production and diversification of antibodies and T-cell receptors via V(D)J recombination in lymphocytes but are absent in simpler eukaryotes such as the yeast Saccharomyces cerevisiae. Here the authors integrate mouse RAG1/2 in S. cerevisiae and demonstrate the ability to create combinatorial diversity starting from a single genetic locus in vivo.

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).

CRISPR-Cas systems, such as type III-A CRISPR-Cas, provide an immune mechanism for prokaryotic hosts to resist parasites, including phages. Here, the authors show that maintenance of conditionally tolerant type III-A systems can affect the fitness of Staphylococcus aureus lysogens.

Andrew Robinson reviews five of the best science picks.

The biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs) involves binding of the N-terminal leader region of precursor peptides to peptide modifying enzymes and subsequent modification of the C-terminal core. Here, the authors describe the intermolecular protein-protein interactions that guide the post translational modification of atypically large and structured RiPP precursor peptides.

Targeted-directed genome mining identified a widespread family of bacterial ClpP-associated clusters whose active products previously eluded detection. One of these clusters from Streptomyces cattleya produces clipibicyclene that selectively inactivates ClpP and may play a role in bacterial competition.

In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa, suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

DNA polymerases are molecular machines that copy genetic material using a template. Here, authors characterize the ability of diverse polymerases to synthesize DNA without a template and show that environmental conditions can alter sequence composition, enabling guided kilobasescale DNA synthesis.

Erythropoiesis can be regulated by transcriptional, epigenetic, and post-transcriptional mechanisms. Here the authors report that N⁶-methyladenosine mRNA methyltransferase complex stimulates erythropoiesis by promoting translation of specific mRNAs.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

A high-throughput method leveraging the Illumina HiSeq platform to screen in the order of 10⁸ individual antibody–antigen interactions within 3 days facilitates the rapid discovery of antibodies to clinically relevant targets.

The growing demand for rare earth elements (REEs) underscores the need for sustainable recovery methods and a reliable supply. Here the authors establish a platform using a yeast to produce bio-oxalic acid for REE recovery, achieving 99% REE recovery from low-grade ore.

Algae hold great promise for biofuel and chemical production but their use as model systems is hampered by the absence of suitable genetic tools. Here Karas et al. present a nuclear episomal vector for diatoms that is maintained in the absence of antibiotics, and a plasmid delivery method via conjugation with E. coli.

Here the authors show that MRAP2 tunes the melanocortin-4 receptor by boosting its G-protein signaling while limiting β-arrestin2 interaction and destabilizing receptor oligomers, shaping appetite regulation.

Widespread declines in common species raise concerns, but links to extinction risk and climate change remain unclear. Here, the authors show that many small climate change effects can accumulate to drive rapid population extinction in a common iconic bird.

Prime-editing mouse models enable the study of specific cancer mutations in vivo.

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.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

Africa-specific genetic variation on chromosome 1 near CHD1L is associated with HIV replication in vivo.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

Becker et. al developed a proteomic proximity labeling platform named POCA, which makes use of a photosensitizer for singlet oxygen production and protein capture in the presence of amine, enabling profiling of interactomes of proteins and lipids in living cells.