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The critical events in transcription termination of RNA polymerase II (Pol II) remain not fully understood. Here, the authors find that the transcription factor Spt5 enhances the activity of RNA exonuclease Xrn2 during transcription to promote efficient termination of transcription.

Cancer cells rely on mitochondria for energy and macromolecule synthesis. Here, the authors show that RNA G-quadruplex dynamics, driven by oncogenic signals, regulate the translation of nuclear-encoded mitochondrial mRNAs, affecting mitochondrial function and promoting cancer cell growth.

Aquatic eDNA-based technologies offer the potential for universal and standardized biodiversity monitoring. In this Perspective, Altermatt et al. discuss how these technologies can help to achieve the targets of the Kunming–Montreal Global Biodiversity Framework through informing appropriate policy and actions, and describe the next steps required for widespread and equitable use of these technologies.

Liver X receptor drives epithelial Areg-mediated intestinal regeneration, while preventing tumour growth through adaptive immune responses.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

The establishment of symbiotic interaction between Aeschynomene evenia and photosynthetic bradyrhizobia doesn’t involve the canonical Nod factors and infection threads. Here, the authors assemble the draft genome of A. evenia and identify a receptor-like kinase in mediating the symbiotic interaction.

GPCR:β-arrestin coupling is a dynamic process modulated by several factors, including membrane lipids. Here, authors show how PI(4,5)P2 favors the coupling of βarrestin 1 to the ghrelin receptor and modulates the arrangement of the resulting complex.

The role of IFN signaling in SARS-CoV-2 infection and outcome is still debated. Here, the authors longitudinally profiled plasma samples from hospitalized patients and show that a persistent inflammatory response is linked to delayed generation of adaptive immunity and increased risk of death when coupled with severe infection.

The acetyltransferases KAT2A and KAT2B are essential regulators of transcription, cell cycle progression and DNA repair. Here the authors describe a KAT2A/2B-dependent acetylome, and show that acetylation of the protein kinase PLK4 contributes to the regulation of centrosome number.

Topical microbicide combined with vaccine effectively prevents infection of female macaques with simian immunodeficiency virus.

Metabolism can influence gene expression through histone modifications. Using a mouse model of the inborn error of metabolism propionic acidaemia, Park et al. show how raised propionate levels produce epigenetic actions that impact cardiac function.

A molecular mechanism for brain-specific angiogenesis operates under the control of Wnt7a/b ligands.

Here the authors find that erythroblasts of myelodysplastic syndromes with SF3B1 mutation leading to inefficient erythropoiesis show DNA replication stress with accelerated forks and reduced R-loops. Restoring R-loops by a histone deacetylase inhibitor rescues erythroid differentiation.

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.

The T cell response to Kaposi sarcoma-associated herpesvirus is critical to controlling infection and immunopathology but has been poorly explored in immunocompetent patients. Here the authors characterise the T cell response to the Kaposi sarcoma-associated herpesvirus proteome in immunocompetent patients from rural Uganda.

Genomic analyses of Klebsiella isolates sampled from multiple human, animal and environmental sources in Northern Italy explore Klebsiella population diversity and show that transmission of multidrug-resistant clones between clinical and environmental settings is scarce.

Modulating pro-inflammatory immune cell kinetics after myocardial infarction is a critical step to prevent heart dysfunction. In this study, the authors show that Ezh2 pharmacological inhibition, acting as an epigenetic checkpoint in monocytes and macrophages, prevents myocardial infarction-induced cardiac dysfunction.

In a prospective international cohort of 1,127 patients with non-small-cell lung cancer and ctDNA-guided therapy, ctDNA detection was associated with shorter survival, independently of clinicopathologic features and metabolic tumor volume.

In this work, authors aim to optimize the dosing of TBI-223, a novel oxazolidinone for tuberculosis, using a translational platform which incorporates preclinical and clinical trial data.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

NKp46 recognizes externalized calreticulin, which translocates from the ER to the cell membrane during ER stress, indicating a danger-associated molecular pattern that eliminates ER-stressed cells.

Leslie Biesecker and colleagues report an exome sequencing study identifying somatic activating mutations in PIK3CA as the cause of a new progressive segmental overgrowth disorder. They identify mutations in PIK3CA in ten additional individuals with overlapping syndromes.

RAG2, a component of the V(D)J recombinase, has a plant homeodomain (PHD) domain which specifically recognizes histone H3 trimethylated at lysine 4 (H3K4me3). A crystal structure of the complex is presented, and the interaction between RAG2 and H3K4me3 shown to be important for V(D)J recombination in vivo.

In mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, malignant progression and metastasis through the activation of a hybrid epithelial-to-mesenchymal transition phenotype.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

Vaccari et al. report that SIV vaccines formulated with two different adjuvants elicit distinct immune responses and effects on SIV acquisition in rhesus macaques.

Zika virus infection during pregnancy can result in birth defects, but underlying pathogenesis at the maternal-fetal interface is unclear. Here, the authors use non-invasive in vivo imaging of Zika-infected rhesus macaques and show that infection results in abnormal oxygen transport across the placenta.

The linear ubiquitination complex (LUBAC) is poorly understood in humans. Casanova and colleagues identify natural mutations in a component of human LUBAC and use this to dissect its function in vivo and in vitro.

Seismic imaging of subducted plates offers a way to improve plate tectonic reconstructions. Here, Braszus et al. use new ocean-bottom seismometer data from the Lesser Antilles to locate subducted spreading centres and faults thus providing a new understanding of the evolution of the Caribbean plate.