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Naderi et al. show that increasing the dispersion of aromatic residues in intrinsically disordered regions of human transcription factors enhances their activity but reduces their specificity.
Zimmermann et al. present OrgaPlexing, an imaging pipeline mapping metabolic organelles and their interactions. They find changes in mitochondria, ER, peroxisome and lipid droplet dynamics that impact macrophage inflammatory lipid mediator synthesis.
Chen et al. perform single-molecule imaging of translation at ribonucleoprotein (RNP) granules. They show that RNP granule surfaces are sites of nanos mRNA translation, whereas the granule interior is translationally repressive.
Agarwal et al. and Wang et al. show that vesicle-associated membrane protein 2 (VAMP2) interacts with and regulates alpha-synuclein biomolecular condensation, affecting α-synuclein function, which may prevent pathological amyloid aggregation.
Agarwal et al. show that vesicle-associated membrane protein 2 interacts with and regulates α-synuclein biomolecular condensation, affecting α-synuclein function, which may prevent pathological amyloid aggregation.
Seehawer et al. show that deletion of Kmt2c or Kmt2d promotes brain metastasis in mouse models of triple-negative breast cancer due to altered KDM6A activity and upregulated MMP3 expression, which may constitute a potential therapeutic target.
Sun, Tao, Han et al. identify the Rabs involved in unconventional protein secretion mediated by TMED10 and in ER–Golgi intermediate compartment organization.
Davidson et al. visualize ferroptosis-like cell death using three-colour live imaging in vivo and demonstrate its role in triggering macrophage recruitment but delaying resolution of inflammation during wounding in the Drosophila embryo.
Harasimov, Gorry, Welp, Penir, Horokhovskyi et al. analyse proteostasis in mammalian oocytes and ovaries: the maintenance of oocytes involves exceptional protein longevity, and many of the extremely long-lived proteins decline as the ovary ages.
Palmulli, Couty and colleagues show that the tetraspanin CD63 promotes accumulation of cholesterol in intraluminal vesicles (ILVs) at the expense of retrieval from endosomes; cholesterol stored in ILVs and exosomes is recovered in an NPC1-dependent manner.
With ultra-deep RNA sequencing, Zhang et al. report increased usage of alternative promoters driven by AR, FOXA1 and MYC during prostate cancer progression and suggest altered DNA methylation as a potential underlying mechanism.
Ma, Cao et al. uncover dynamic changes of chromatin reorganization in progenitor B cells during ageing, associated with altered H3K27ac levels and expression of genes that are critical for B cell development.
With a shRNA targeted screen, Ferrer, Cho, Boon et al. identify a role for Gstt1 in enhancing epithelial–mesenchymal transition and disseminated tumour cell features in a subset of slow-cycling cells, thereby facilitating metastatic progression.
Wu, Zhao, Shin and Yin show that the RNA–RNA-binding protein complex LOC–DHX15 drives microglia infiltration into the tumour microenvironment in glioblastoma and suggest targeting this complex as a potential treatment strategy.
El-Hachem et al. show that MAPK therapy upregulates valine aminoacyl-tRNA synthetase and alters fatty acid oxidation by promoting translation of valine-enriched transcripts, providing a resistance mechanism that may be therapeutically targeted.
Batki, Hetzel et al. report a lineage-tracing strategy to track extraembryonic gut endoderm cells over development. They find that these cells are eventually eliminated in a p53-dependent manner and neighbouring embryonic cells clear their remnants.
Liu, Xie and colleagues profile putative cis-regulatory elements in mouse oocytes and pre-implantation embryos. They further validate putative enhancers in oocytes and identify the transcription factors TCF3 and TCF12 as key regulators of folliculogenesis.
Jungnickel, Guelle et al. use metabolomics, electrophysiology and cryo-EM approaches to show that MFSD1 is a lysosomal dipeptide uniporter, which provides an additional route to recycle lysosomal proteolysis products to lysosomal amino acid exporters.
Machitani, Nomura and colleagues report that hTERT suppresses R-loops through its RNA-dependent RNA polymerase activity and protects against genome instability.