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Shi, Zhou, Xuan, Jiang et al. identify a population of CD8+ T cells that migrate from bone marrow to the small intestine during leukaemogenesis and then traffic back to contribute to anti-leukaemia immune responses during chemotherapy treatment.
Mutations in the gene encoding the E3 ubiquitin ligase TRIAD3A cause adult-onset neurodegenerative disorders. We reveal that the ubiquitin ligase activity of TRIAD3A promotes its liquid–liquid phase separation. TRIAD3A co-partitions with tau into droplets, where tau forms fibrillar aggregates. TRIAD3A mediates the degradation of these aggregates through its role as an autophagy adaptor.
Werbowetski-Ogilvie, Taylor and colleagues report a noncanonical role for OTX2 in regulating alternative splicing and controlling a stem cell and pro-tumorigenic splicing program in group 3 medulloblastoma.
Zhou et al. show that the E3 ubiquitin ligase TRIAD3A assembles into liquid–liquid phase-separated droplets that contain tau and promote conversion to fibrillar aggregates and tau autophagic degradation.
Schwab, Rao et al. report that Zeb1 mediates enhanced ferroptosis sensitivity in cancer cells after EMT activation, associated with altered expression of selected lipogenic enzymes and an subsequent increase in the PUFA:MUFA ratio.
Zhou, Jiang, Dai et al report that upon ultraviolet-C radiation, full-length GSDME can induce pyroptosis without cleavage, likely due to conformational change and oxidative oligomerization after increased PARylation and mitochondrial lipid ROS levels.
Cai et al. show that, in lysosomes under hydrostatic pressure in macrophages, lysosomal mechanosensitive channels cause a cation leak. This leads to the inhibition of mTORC1, activation of TFEB/TFE3 and release of monocyte chemoattractant proteins.
Jiang et al. document an abundance of neutrophil-derived migrasomes in the blood of mice and humans and show that migrasomes are enriched in coagulation factors, accumulate at sites of injury and trigger platelet activation and clot formation.
The role of RNA in preserving the integrity and dynamics of membrane-bound organelles remains largely unexplored. A study now identifies the Golgi-resident protein GM130 as an RNA-binding protein that scaffolds the Golgi ribbon in a polyadenylated-RNA-dependent manner.
Zhang and Seemann show that GM130 forms a complex with RNA-binding proteins. RNA binding of GM130 induces liquid–liquid phase separation and these co-condensates function to link the Golgi ribbon.
In two independent studies, Sun, Liu et al. and Sun et al. develop SPATAC-seq to map the chromatin accessibility landscape of zebrafish embryogenesis and mouse organogenesis, respectively, and identify transcription regulators that determine cell fate.
In two independent studies, Sun, Liu et al. and Sun et al. develop SPATAC-seq to map the chromatin accessibility landscape of zebrafish embryogenesis and mouse organogenesis, respectively, and identify transcription regulators that determine cell fate.
Transcription factors (TFs) and cis-regulatory elements (CREs) drive organism development. Suboptimal binding of TFs to CREs is shown to be key for the specificity of gene expression. New work now indicates that a similar principle governs the activities of TFs and their regulatory specificity.
Cellular organelles form an interconnected and dynamic network that orchestrates cellular functions. Using a multispectral imaging and computational analysis approach (‘OrgaPlexing’), a study now identifies multi-organelle units as crucial regulators of metabolic reprogramming in primary macrophages upon inflammatory stimuli.
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.
Qin, Liu and colleagues develop a tool that combines CRISPR technology with G-quadruplex (G4)-stabilizing protein or ligand to specifically target DNA G4 structures. This tool provides better understanding of G4 functions and enables G4-based drug development.
The subcellular localization of numerous mRNAs has been demonstrated. This Review presents the different means of mRNA localization described and discusses how they can account for the widespread occurrence of this phenomenon.