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By regulating the condensation of the molecular transport machinery coat protein complex II (COPII), manganese ions contribute to the regulation of lipoprotein secretion and thereby the circulating lipid levels.
The main barriers for intracellular receptors to sense circulating pathogen-associated molecular patterns (PAMPs) is how these PAMPs enter the cells. A study reveals that extracellular vesicles (EVs) bind lipopolysaccharide (LPS) via the lipid bilayer and mediates LPS intracellular transfer in a CD14-dependent endocytosis to activate noncanonical NLRP3 inflammasome and pyroptosis.
Cells use diverse mechanisms to rid themselves of dysfunctional or excess mitochondria. A study now shows that C. elegans sperm use a previously undescribed mechanism to rapidly expel single healthy mitochondria in membrane-bound structures called mitophers.
YTHDF family members are ‘readers’ of a common mRNA modification, but their effects on mRNA translation and stability have been disputed. A new study shows that YTHDF1 and YTHDF3 are post-translationally regulated through O-GlcNAcylation, unifying disparate results and pointing to environmental cues that could modulate YTHDF function.
How spatial organization in the cell is achieved on the organelle scale is unclear. A new study finds that tethering specific proteins near the surface of micelle-like paraspeckles modifies their properties and determines whether these subnuclear organelles are separate from, adhere to, or are engulfed by nuclear speckles.
The bacterial pathogen Legionella pneumophila uses effectors — toxins — to facilitate pathogenesis within host cells. A recent study identifies dual mechanisms of the effector SidI as an inhibitor of translation elongation. The N-terminal domain mimics tRNA, whereas the C-terminal domain glycosylates the ribosome.
Disruption of ribosome assembly results in the accumulation of aggregation-prone ‘orphaned’ ribosomal proteins that are toxic to cells if left unchecked. A study finds that cells store such ribosomal proteins during heat shock to enable a quick recovery of ribosome assembly after the removal of this stress.
The fibrous geometry of extracellular matrices (ECMs) is believed to facilitate cell adhesion, but a mechanistic link is lacking. We uncover a type of integrin-mediated cell adhesion — ‘curved adhesion’ — driven by the fibrous geometry of the ECM. Curved adhesions are induced by membrane curvature, enabling cell adhesion to soft three-dimensional (3D) ECM fibres.
Bone marrow endothelial cells deliver oxygen and nutrients and regulate bone formation and haematopoiesis in the surrounding microenvironment. A new study identifies a subtype of capillary that occurs exclusively in the epiphysis and displays unique characteristics that have a role in balancing osteogenesis and haematopoiesis.
ESCRT-III seals holes in the nuclear envelope (NE). A study now shows that the Cmp7-directed ESCRT-III cascade that grommets and reseals NE holes after spindle pole body (SPB) extrusion at the end of fission yeast mitosis is complemented by the presence of a proteinaceous diffusion barrier to ensure NE integrity.
In many species, maternally deposited Piwi-interacting RNAs (piRNAs) deliver intergenerational epigenetic information to protect progeny from transposon expansion or invasion. However, Y-chromosome-encoded piRNAs cannot be passed from mothers to male offspring, yet mothers use autosomally encoded piRNAs to allow sons to utilize their Y chromosome to protect against ‘selfish’ elements.
The molecular program of human germline commitment remains largely unknown. A new study delineates the multifaceted functions of DMRT1 in human germline development, particularly in the transition from early to late primordial germ cells.
RNA modifications have emerged as key gene regulators. A new study shows that increased levels of reactive oxygen species in cancer induce widespread, sequence-specific modifications of guanines in the seed regions of microRNAs, altering the targets of those miRNAs and influencing tumorigenesis.
Embryonic diapause in development and paused pluripotency in embryonic stem cells result in a state of hypotranscription through mechanisms that remain unclear. A new study dissects the role of METTL3-deposited global m6A RNA methylation in mediating this transcriptional dormancy.
Genetic clearance of p16high senescent cells or the use of senolytics improved the efficacy of stem cell reprogramming in vitro and in vivo, and helped establish induced pluripotent stem cells with features of experimental totipotency. When ablation of p16high senescent cells was combined with partial four-factor reprogramming in vivo, we observed noticeable histopathological liver rejuvenation in aged mice.
Pathways linked to the modification of RNA with N6-methyladenosine (m6A) are known to be involved in initiating and maintaining cancer. But many of the key components of these pathways remain undiscovered. The RBFOX2 protein has now been identified as an m6A reader involved in locus-specific chromatin regulation, with therapeutic implications for myeloid leukaemia.
The interaction of non-immune and immune cells in the tumour microenvironment (TME) determines the quality of the immune attack on nascent tumour cells. A new study in melanoma cells shows that specific histone variants dampen the expression of cytokine genes in cancer-associated fibroblasts, leading to an immunosuppressive TME.
The mechanisms controlling lysosome abundance in cells and how changes in lysosome pool size impact physiological and pathophysiological processes are discussed.
Cells use various metabolic pathways to synthesize the building blocks for growth and proliferation. To ensure balanced growth, these biosynthetic processes must be tightly coordinated. We describe a molecular machinery that senses the cellular capacity to make lipids to regulate other biosynthetic processes — such as protein synthesis — accordingly.
A fast protocol for chemical cellular reprogramming reveals a diapause-like state, endogenous retrovirus activation and barriers to cell-fate transitions on the way to pluripotency. The system offers insights into manipulation of cellular regeneration and rejuvenation, two processes with great therapeutic potential.
