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miRNAs are loaded into Argonaute protein and repress complementary mRNA targets. Here the authors show the unappreciated role of RNA binding proteins for efficient miRNA targeting and expand the current understanding of miRNA targeting.

The immunosuppressive role of regulatory T (Treg) cells largely depends on their virtue of expressing the transcription factor FOXP3. Here the authors show that the E3 deubiquitinase USP21 stabilizes FOXP3 by mediating its deubiquitination and helps to maintain the expression of Treg signature genes and Treg lineage stability in mice.

Docosahexaenoic acid is a major and important retinal fatty acid that is recruited and retained in the photoreceptor membrane via an unknown mechanism. Here, Rice et al. show that adiponectin receptor 1 is a key molecular switch for docosahexaenoic acid membrane homeostasis and photoreceptor cell function.

Mixed tailing of hepatitis B virus and human cytomegalovirus transcripts via recruitment of the TENT4–ZCCHC14 complex by a common RNA element protects viral RNAs from degradation.

Occurrence of DNA double-strand break (DSB) repair is important for genome integrity. Here, the authors reveal that Pellino1 is a DSB-responsive ubiquitin ligase required for promoting the accumulation of ATM and MRN complex at DSB sites via NBS1 ubiquitination.

p53 regulates signalling pathways involved in metabolic homeostasis. Here the authors show that O-GlcNAcylation of p53 in the liver plays a key role in the physiological regulation of glucose homeostasis, potentially via controlling the expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase.

Metabolic rewiring of cytotoxic T lymphocytes (CTLs) can impair their antitumor functions. Sun and colleagues demonstrate that CTL-intrinsic activity of the kinase NIK is essential for CTL metabolic fitness in the tumor microenvironment.

Adenine nucleotide translocase (ANT) 2 promotes ADP/ATP exchange across the mitochondrial inner membrane. Choet al. show that liver specific Ant2 deletion increases uncoupled respiration and protects mice against fatty liver and obesity-induced insulin resistance.

PHD2-mediated pseudohypoxia, rather than ambient hypoxia, safeguards a balanced mesendoderm specification, relying on the HIF1α-regulated Wnt/β-catenin pathway.

Kim et al. reveal that TFEB expression is protective in the setting of diet-induced obesity by activating the expression of GDF15 in adipose tissue macrophages in mice and humans.

LUBAC is involved in adding linear ubiquitin chains to important immune signaling proteins. Here the authors show that this mechanism is effective in inhibiting STAT1-mediated interferon signaling, and that the deubiquitinase OTULIN can remove these linear ubiquitins from STAT1 to reactivate this antiviral signaling pathway.

Radiotherapy is the main treatment for most cancer, but it is unclear if targeting tumour vasculature can enhance tumour radiosensitivity. Here, the authors show that tumour endothelial-mesenchymal transition after radiotherapy leads to proliferation of radioresistant CSCs and tumour associated macrophages polarization.

Kin selection predicts female-biased sex ratios in haplodiploid eusocial insects because sisters are more related to each other than to their brothers. Here the authors provide evidence that sex ratio bias also occurs in diploid eusocial insects, which do not show asymmetric relatedness.

Studying the specific roles of macrophage subsets has been hampered by a lack of subset-specific probes. Here the authors report an M1 selective fluorescent probe named CDr17, and demonstrate the suitability of this probe for tracking M1 macrophages in vivo.

How STING agonists exert anti-tumour effects remains unclear. Here, the authors show that STING agonists suppress tumor growth of subcutaneous xenografts models inducing early apoptosis of endothelial cells through the TNFalpha-TNFR1 signaling, while in primary tumors, additional inhibition of AKT is required for efficient induction of apoptosis via the same pathway.

Impairments of cerebellar-dependent motor control and learning are implicated in some forms of autism spectrum disorder (ASD). In this study, the authors provide a characterization of the motor deficits and cerebellar function abnormalities in a transgenic mouse model of ASD.

Proteomics in the hippocampal dentate gyri reveal that behavioural impairments in THRSP-overexpressing mice could be regulated by Wnt signalling.

Coronaviruses exploit the host caspase-6 to cleave coronavirus nucleocapsid protein into fragments with interferon-antagonizing activity to facilitate virus replication.

Interorgan communications play key roles in the regulation of whole-body energy metabolism. Here, the authors report the myokine Musclin as a negative regulator of beige adipose thermogenesis and systemic energy homeostasis through Tfr1/PKA signalling mediated muscle fat crosstalk.

Mutations in LRRK2 kinase are associated with Parkinson’s disease. Here the authors show that LRRK2 modulates propagation of α-synuclein, using rodent and C. elegans models, and show that this is dependent on phosphorylation of one of its substrates, RAB35.

Huang et al. show that, in response to chemotherapy, PTEN directly interacts with NLRP3 in myeloid cells to enhance inflammasome activation and antitumour immune responses.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Adipocyte tissue macrophages (ATM) are recruited and activated in obesity. The authors show that adipocytes release lactate as a signal of inflammation and that this metabolite can enhance obesity associated inflammation through stimulation of ATM by direct binding with PHD2.

The authors provide insight into fundamental mechanisms of gene regulation that carries therapeutic implications for Prader-Willi syndrome and a model for maintenance of the PWS imprinted domain.

Chromosome-scale and haplotype-resolved assembly of Pinus densiflora sheds light on Pinus-specific genome enlargement. Comparison between haplotypes and resequencing of 30 wild accessions show allelic imbalance with roles in flowering regulation and stress resistance.

Jung-Eun Lee et al. show that aged mice have increased oxidative stress and NADPH activity in the hippocampus which is associated with increased susceptibility to stress. Upregulation of NADPH oxidase, due to sustained p47phox expression, was caused by a decrease in SUV39H1 levels, highlighting an important mechanism regulating aging-induced stress susceptibility.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Excessive NLRP3 inflammasome activation underlies inflammatory diseases such as gout. Here the authors show that orphan nuclear receptor small heterodimer partner protein (SHP) negatively regulates NLRP3, and its loss leads to accumulation of damaged mitochondria and gout-like immunopathology.

Deubiquitinases (DUBs) targeting Met1-linked ubiquitin chains have important functions in mammals but are barely studied in plants. Here, the authors identify rice OTUB1 as a Met1-targeting DUB, characterize the structural determinants of this activity, and show that these features are conserved in green plants.