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Ye et al. define the structure and mechanisms of a bacterial pathway that performs ubiquitination-like protein conjugation, revealing new insights into the evolution and biological roles of ubiquitination pathways across kingdoms.

SCEP3 is a new synaptonemal complex protein that prevents clustering of crossovers during meiosis in Arabidopsis, so that every pair of homologous chromosomes receives at least one ‘obligate’ crossover.

Viruses generally have compact genomes, resulting in many viral mRNAs with short 5’ untranslated regions. An antiviral complex exploits this feature of viral mRNAs to selectively inhibit viral protein synthesis and repress viral replication.

Immunization of macaques with nanoparticle-conjugated receptor-binding domain of SARS-CoV-2 adjuvanted with 3M-052 and alum results in cross-neutralizing antibodies against bat coronaviruses, SARS-CoV and SARS-CoV-2 variants, and may provide a platform for developing pan-coronavirus vaccines.

The authors have previously demonstrated the neutralising capacity of their nanoparticle vaccine, as well as showing protection of non-human primates from SARS-CoV-2 WA-1 infection. In this work, they investigate the ability of their vaccine candidate to neutralise SARS-CoV-2 variants of concern, and protect animals from other sarbecoviruses.

Retrieving interactions between RNA-binding proteins (RBPs) and RNA in endogenous biological contexts remains challenging. Here, the authors develop INSCRIBE (IN situ Sensitive Capture of RNA-protein Interactions in Biological Environments), which enables highly specific RNA-binding site identification across diverse biological samples.

Blockade of cIAP1 and cIAP2 induces a tumor cell-autonomous type-I IFN response that activates myeloid cells and potentiates anti-tumor immunity in pre-clinical models and patients with multiple myeloma.

The malaria parasite Plasmodium falciparum utilizes thiamine for the production of essential enzymatic cofactors. Chan et al. show that inhibition of thiamine utilization with oxythiamine inhibits proliferation of P. falciparumand reduces parasite growth in a mouse model of malaria infection.

Bellaart et al. address how the ubiquitin ligase tripartite motif-containing protein 37, the gene for which is mutated in Mulibrey nanism, uses peptide motif recognition and substrate-directed oligomerization to prevent the formation of ectopic spindle poles that cause chromosome missegregation.

The main function of the mammary gland is to produce milk to sustain offspring. Here, the authors show that secretory alveolar cells in the lactating gland in several species are binucleated, which increases milk production, and that binucleation is regulated by Aurora kinase-A and Polo-like kinase-1.

The bacterial phage anti-restriction-induced system, PARIS, operates as a toxin–antitoxin system, in which the antitoxin AriA sequesters and inactivates the toxin AriB until triggered by the T7 phage counterdefence protein Ocr.

The enzyme SPO11 has a crucial role in meiosis, the process that forms sperm and egg cells. The activity of purified SPO11 has now been reconstituted in a cell-free system — enabling the enzyme’s role to be studied in detail.

mRNA-1273, an mRNA vaccine that encodes a stabilized prefusion-state severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, elicits robust immune responses and protects mice against replication of SARS-CoV-2 in the upper and lower airways.

This study demonstrates that bacteria use a ubiquitin transferase-like enzyme to prime cGAS/DncV-like nucleotidyltransferase activation and use a deubiquitinase-like enzyme to decrease activity. 

A study reports the structure and molecular mechanism of the Bil anti-phage defence system, demonstrating that it is the closest prokaryotic homologue of canonical eukaryotic ubiquitination pathways.

A family of large-genome bacteriophages assembles a protective protein shell around its replicating DNA called the ‘phage nucleus’. Here, Enustun et al. use proteomics to identify a set of proteins associated with the phage nucleus that aid macromolecule transport through the nuclear shell.

Comparative Hi-C analysis of synchronized mouse spermatocyte populations reveals dynamic changes in chromosome organization during meiotic prophase that permit homolog pairing while sustaining gene expression.

The nucleus-like compartment formed in bacteria during infection by jumbo phage 201phi2-1 is composed of the bacteriophage protein chimallin, which can self-assemble into closed compartments in vitro.

The beta variant (B.1.351) is to date the most resistant to neutralization of the SARS-CoV-2 variants. Using nonhuman primates, Seder and colleagues demonstrate that double vaccination with a high dose of the lipid nanoparticle vaccine mRNA-1273 protects against infection with the beta variant.

The mitotic checkpoint complex (MCC) is assembled during both mitosis and interphase. Here, the authors use auxin-inducible degron tags to rapidly degrade TRIP13 and find that mitotic exit requires MCC disassembly by TRIP13-catalyzed removal of Mad2 or APC1-driven ubiquitination of Cdc20.

The authors conduct mass spectrometry experiments identifying H3K4me1-associated proteins, including members of the BAF chromatin-remodeling complex. They show that H3K4me1 augments association of the BAF complex with enhancers in vivo and that H3K4me1-marked nucleosomes are more efficiently remodeled by the BAF complex in vitro.

The exchange of DNA between pairs of chromosomes is key to sexual reproduction. It emerges that one step in this process — the introduction of DNA breaks by the enzyme Spo11 — relies on condensation of proteins into liquid-like droplets.

The SARS-CoV-2 spike ectodomain is destabilized by cold temperature storage, an effect that can be reversed by incubation at 37 °C or by stabilizing its conformation in the ‘down’ state.

The SARS-CoV-2 nucleocapsid (N) protein binds the viral RNA genome and contains two ordered domains flanked by three intrinsically-disordered regions. Here, the authors show that RNA binding induces liquid-liquid phase separation of N, which is driven by its central intrinsically-disordered region and is modulated by phosphorylation. The SARS-CoV-2 Membrane (M) protein also phase-separates with N, and three-component mixtures of N + M + RNA form mutually exclusive compartments containing N + M or N + RNA.

The validation and analysis of X-ray crystallographic data is essential for reproducibility and the development of crystallographic methods. Here, the authors describe a repository for crystallographic datasets and demonstrate some of the ways it could serve the crystallographic community.

Here, the authors characterize tissue-level SARS-CoV-2 infection and pathogenesis in transgenic mice expressing human angiotensin converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18-hACE2) and show that infection induces lethality, making the K18-hACE2 model suitable for vaccine and therapeutic evaluation.

New World hemorrhagic fever arenaviruses are rodent transmitted agents that cause severe, often fatal human disease. The structure of the Machupo virus glycoprotein 1 subunit in complex with its human cellular receptor, transferrin receptor 1, was solved. The interaction interfaces between the two proteins and sequence alignments suggest that these viruses fortuitously acquired the ability to bind human transferrin receptor 1 while adapting to their natural hosts.

Alternative expression analysis by sequencing (ALEXA-seq) aligns RNA-seq reads from different cell types to a database of alternative expression sequence features and quantifies isoforms that are differentially expressed between samples.

In a new study including 200 families who experienced perinatal death, adding genomic analyses to standard autopsies improved the identification of underlying pathogenic causes and informed genetic counseling.

New data collection methods enable ab initio protein structure determination by micro-electron diffraction for the first time.

Marra and colleagues describe POG570, a pan-cancer, whole-genome, transcriptome and clinical dataset stressing the molecular interactions in advanced and post-therapy cancer patients.

An investigation of tau’s phase separation propensity and interactions with DNA, nucleosome arrays, and heterochromatin proteins shows that these properties are dependent on tau’s phosphorylation state.

The Human BioMolecular Atlas Program (HuBMAP) presents its production phase: the generation of spatial maps of functional tissue units across organs from diverse populations and the creation of tools and infrastructure to advance biomedical research.